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Animals rely on a balance of endogenous and exogenous sources of immunity to mitigate parasite attack. Understanding how environmental context affects that balance is increasingly urgent under rapid environmental change. In herbivores, immunity is determined, in part, by phytochemistry which is plastic in response to environmental conditions. Monarch butterflies Danaus plexippus, consistently experience infection by a virulent parasite Ophryocystis elektroscirrha, and some medicinal milkweed (Asclepias) species, with high concentrations of toxic steroids (cardenolides), provide a potent source of exogenous immunity. We investigated plant-mediated influences of elevated CO2 (eCO2 ) on endogenous immune responses of monarch larvae to infection by O. elektroscirrha. Recently, transcriptomics have revealed that infection by O. elektroscirrha does not alter monarch immune gene regulation in larvae, corroborating that monarchs rely more on exogenous than endogenous immunity. However, monarchs feeding on medicinal milkweed grown under eCO2 lose tolerance to the parasite, associated with changes in phytochemistry. Whether changes in milkweed phytochemistry induced by eCO2 alter the balance between exogenous and endogenous sources of immunity remains unknown. We fed monarchs two species of milkweed; A. curassavica (medicinal) and A. incarnata (non-medicinal) grown under ambient CO2 (aCO2 ) or eCO2 . We then measured endogenous immune responses (phenoloxidase activity, haemocyte concentration and melanization strength), along with foliar chemistry, to assess mechanisms of monarch immunity under future atmospheric conditions. The melanization response of late-instar larvae was reduced on medicinal milkweed in comparison to non-medicinal milkweed. Moreover, the endogenous immune responses of early-instar larvae to infection by O. elektroscirrha were generally lower in larvae reared on foliage from aCO2 plants and higher in larvae reared on foliage from eCO2 plants. When grown under eCO2 , milkweed plants exhibited lower cardenolide concentrations, lower phytochemical diversity and lower nutritional quality (higher C:N ratios). Together, these results suggest that the loss of exogenous immunity from foliage under eCO2 results in increased endogenous immune function. Animal populations face multiple threats induced by anthropogenic environmental change. Our results suggest that shifts in the balance between exogenous and endogenous sources of immunity to parasite attack may represent an underappreciated consequence of environmental change.

Quantitative PCR (qPCR) has been commonly used to measure gene expression in a number of research contexts, but the measured RNA concentrations do not always represent the concentrations of active proteins which they encode. This can be due to transcriptional regulation or post‐translational modifications, or localization of immune environments, as can occur during infection. However, in studies using free‐living non‐model species, such as in ecoimmunological research, qPCR may be the only available option to measure a parameter of interest, and so understanding the quantitative link between gene expression and associated effector protein levels is vital.Here, we use qPCR to measure concentrations of RNA from mesenteric lymph node (MLN) and spleen tissue, and multiplex ELISA of blood serum to measure circulating cytokine concentrations in a wild population of a model species, Mus musculus domesticus.Few significant correlations were found between gene expression levels and circulating cytokines of the same immune genes or proteins, or related functional groups. Where significant correlations were observed, these were most frequently within the measured tissue (i.e., the expression levels of genes measured from spleen tissue were more likely to correlate with each other rather than with genes measured from MLN tissue, or with cytokine concentrations measured from blood).Potential reasons for discrepancies between measures including differences in decay rates and transcriptional regulation networks are discussed. We highlight the relative usefulness of different measures under different research questions and consider what might be inferred from immune assays., In wild house mice, there is little correlation between immune gene expression and final proteins. This is important to consider in future ecoimmunology research.

Exposure to stressors over prolonged periods can have fitness-relevant consequences, including suppression of immune function. We tested for effects of presence of an invasive species threat on a broad panel of immune functions of a coexisting lizard. Eastern fence lizards (Sceloporus undulatus) have been exposed to invasive fire ants (Solenopsis invicta) for over 80 years. Fire ants sting and envenomate lizards, causing physiological stress, but we do not have a comprehensive understanding of the broad immune consequences of lizard exposure to fire ant presence. We conducted a suite of immune measures on fence lizards caught from areas with long histories of fire ant invasion and lizards from areas not yet invaded by fire ants. The effect of fire ant presence on immunity varied depending on the immune component measured: within fire ant invaded areas, some portions of immunity were suppressed (lymphocytic cell-mediated immunity, complement), some were unaffected (phagocytic respiratory burst, natural antibodies), and some were enhanced (anti-fire ant immunoglobulin M, basophils) compared to within uninvaded areas. Rather than fire ants being broadly immunosuppressing, as generally assumed, the immune response appears to be tailored to this specific stressor: the immune measures that were enhanced are important to the lizards' ability to handle envenomation, whereas those that were unaffected or suppressed are less critical to surviving fire ant encounters. Several immune measures were suppressed in reproductive females when actively producing follicles, which may make them more susceptible to immunosuppressive costs of stressors such as interactions with fire ants.

IN FOCUS Becker, D. J., Albery, G. F., Kessler, M. K., Lunn, T. J., Falvo, C. A., Czirjak, G. A., Martin, L. B., & Plowright, R. K. (2020). Macroimmunology: The drivers and consequences of spatial patterns in wildlife immune defence. Journal of Animal Ecology, 89, 972-995. Ecoimmunology seeks to identify and explain natural variation in immune function. Most research so far has focused on differences among individuals within populations, which are often driven by trade-offs in resource allocation between energetically costly immunity and competing processes such as reproduction. In their review article, Becker et al. (2020) have proposed a framework to explicitly address habitat- and population-level differences in wildlife immune phenotypes. Termed macroimmunology, this concept integrates principles from ecoimmunology and macroecology. Becker et al. (2020) have highlighted three non-mutually exclusive habitat features that are likely to vary at spatial scales and influence immune function: (a) parasite pressure, (b) abiotic and biotic factors and (c) anthropogenic changes. However, a large and robust body of literature suitable for synthesis to detect macroimmunology patterns and effect sizes is not yet available. Through their systematic review and critical assessment, Becker et al. (2020) identified common problems in existing research that hinders spatial inferences, such as a need for spatial replication in study design and statistical analyses that account for spatial dependence. Overall, macroimmunology has the potential to identify and even predict spatial patterns in immune phenotypes that form the mechanistic underpinnings of important wildlife disease processes, and this review represents an important step to realizing these goals.

Understanding host immune function and ecoimmunology is increasingly important at a time when emerging infectious diseases (EIDs) threaten wildlife. One EID that has emerged and spread widely in recent years is chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), which is implicated unprecedented amphibian declines around the world. The impacts of Bd have been severe for many amphibian species, but some populations have exhibited signs of persistence, and even recovery, in some regions. Many mechanisms may underpin this pattern and amphibian immune responses are likely one key component. Although we have made great strides in understanding amphibian immunity, the complement system remains poorly understood. The complement system is a nonspecific, innate immune defense that is known to enhance other immune responses. Complement activation can occur by three different biochemical pathways and result in protective mechanisms, such as inflammation, opsonization, and pathogen lysis, thereby providing protection to the host. We currently lack an understanding of complement pathway activation for chytridiomycosis, but several studies have suggested that it may be a key part of an early and robust immune response that confers host resistance. Here, we review the available research on the complement system in general as well as amphibian complement responses to Bd infection. Additionally, we propose future research directions that will increase our understanding of the amphibian complement system and other immune responses to Bd. Finally, we suggest how a deeper understanding of amphibian immunity could enhance the conservation and management of amphibian species that are threatened by chytridiomycosis., The fungal pathogen Batrachochytrium dendrobatidis (Bd), is implicated in worldwide amphibian declines. The complement system is a nonspecific, innate immune defense that is known to enhance other immune responses. Here, we address what is known about the complement system in amphibians and how it may respond to infection with Bd., Highlights The complement system is an immune component present in vertebrates, but little is known about its role in amphibian chytridiomycosis.We review recent research, current gaps in knowledge, and we suggest future research to fill these gaps.

Synopsis One of the key foci of ecoimmunology is understanding the physiological interactions between reproduction and immune defense. To assess an immune challenge, investigators typically measure an immune response at a predetermined time point that was selected to represent a peak response. These time points often are based on the immunological responses of nonreproductive males. Problematically, these peaks have been applied to studies quantifying immune responses of females during reproduction, despite the fact that nonreproductive males and reproductive females display fundamentally different patterns of energy expenditure. Previous work within pharmacological research has reported that the response to the commonly-used antigen keyhole limpet hemocyanin (KLH) varies among individuals and between females and males. In this heuristic analysis, we characterize antibody responses to KLH in females with varying reproductive demands (nonreproductive, lactating, concurrently lactating, and pregnant). Serum was taken from one animal per day per group and assessed for general and specific Immunoglobulins (Igs) G and M. We then used regression analysis to characterize the antibody response curves across groups. Our results demonstrate that the antibody response curve is asynchronous among females with varying maternal demands and temporally differs from the anticipated peak responses reflected in standardized protocols. These findings highlight the importance of multiple sampling points across treatment groups for a more integrative assessment of how reproductive demand alters antibody responses in females beyond a single measurement.

When animals are faced with a life-threatening challenge, they mount an organism-wide response (i.e. Plan A). For example, both the stress response (i.e. fight-or-flight) and the immune response recruit molecular resources from other body tissues, and induce physiological changes that optimize the body for defense. However, pathogens and predators often co-occur. Animals that can optimize responses for a dual challenge, i.e. simultaneous predator and pathogen attacks, will have a selective advantage. Responses to a combined predator and pathogen attack have not been well studied, but this paper summarizes the existing literature in insects. The response to dual challenges (i.e. Plan B) results in a suite of physiological changes that are different from either the stress response or the immune response, and is not a simple summation of the two. It is also not a straight-forward trade-off of one response against the other. The response to a dual challenge (i.e. Plan B) appears to resolve physiological trade-offs between the stress and immune responses, and reconfigures both responses to provide the best overall defense. However, the dual response appears to be more costly than either response occurring singly, resulting in greater damage from oxidative stress, reduced growth rate, and increased mortality.

Cane toads (Rhinella marina) were introduced worldwide and have become invasive in multiple locations, representing a major driver of biodiversity loss through competition (food, shelter, territory), predation, and the poisoning of native species. These toads have been used in Australia as a model for studies concerning invasion biology and ecoimmunology, as longer-established (core) and invasion front (edge) populations show altered stress and immune response profiles. Although cane toads were also introduced into the United States in the 1950s, these patterns have yet to be evaluated for the populations spanning Florida. Toads introduced into Florida have dispersed primarily northward along a latitudinal gradient, where they encounter cooler temperatures that may further impact stress and immune differences between core and edge populations. In this study, we sampled cane toads from nine different locations spanning their invasion in Florida. Cane toads from southern populations showed higher plasma bacterial killing ability and natural antibody titers than the toads from the northern populations, indicating they have a better immune surveillance system. Also, southern toads were more responsive to a novel stressor (1 hr restraint), showing a higher increase in corticosterone levels. These results indicate that possible trade-offs have occurred between immune and stress responses as these toads have become established in northern cooler areas in Florida.

The prevalence and intensity of parasites in wild hosts varies across space and is a key determinant of infection risk in humans, domestic animals, and threatened wildlife. Because the immune system serves as the primary barrier to infection, replication, and transmission following exposure, we here consider the environmental drivers of immunity. Spatial variation in parasite pressure, abiotic and biotic conditions, and anthropogenic factors can all shape immunity across spatial scales. Identifying the most important spatial drivers of immunity could help preempt infectious disease risks, especially in the context of how large-scale factors such as urbanization affect defense by changing environmental conditions. We provide a synthesis of how to apply macroecological approaches to the study of ecoimmunology (i.e., macroimmunology). We first review spatial factors that could generate spatial variation in defense, highlighting the need for large-scale studies that can differentiate competing environmental predictors of immunity and detailing contexts where this approach might be favored over small-scale experimental studies. We next conduct a systematic review of the literature to assess the frequency of spatial studies and to classify them according to taxa, immune measures, spatial replication and extent, and statistical methods. We review 210 ecoimmunology studies sampling multiple host populations. We show that whereas spatial approaches are relatively common, spatial replication is generally low and unlikely to provide sufficient environmental variation or power to differentiate competing spatial hypotheses. We also highlight statistical biases in macroimmunology, in that few studies characterize and account for spatial dependence statistically, potentially affecting inferences for the relationships between environmental conditions and immune defense. We use these findings to describe tools from geostatistics and spatial modeling that can improve inference about the associations between environmental and immunological variation. In particular, we emphasize exploratory tools that can guide spatial sampling and highlight the need for greater use of mixed-effects models that account for spatial variability while also allowing researchers to account for both individual- and habitat-level covariates. We lastly discuss future research priorities for macroimmunology, including focusing on latitudinal gradients, range expansions, and urbanization as being especially amenable to large-scale spatial approaches. Methodologically, we highlight critical opportunities posed by assessing spatial variation in host tolerance, using metagenomics to quantify spatial variation in parasite pressure, coupling large-scale field studies with small-scale field experiments and longitudinal approaches, and applying statistical tools from macroecology and meta-analysis to identify generalizable spatial patterns. Such work will facilitate scaling ecoimmunology from individual- to habitat-level insights about the drivers of immune defense and help predict where environmental change may most alter infectious disease risk.

Energy allocation trade‐offs associated with mounting metabolically costly immune responses may serve as sublethal mechanisms by which pathogens reduce host fitness. The emergence of cutaneous fungal pathogens, which invade the skin of their host and have the potential to disturb energy and water balance, highlight the importance of host physiology in determining individual‐ and population‐level effects of disease. Snake fungal disease (SFD, ophidiomycosis), caused by the fungal pathogen Ophidiomyces ophiodiicola (Oo), is an emerging disease afflicting wild snake populations throughout eastern North America. Emaciation and dehydration are phenotypic correlates of SFD, but it is unknown if such declines in host condition occur via effects of Oo infection on host physiology (i.e. increased rates of metabolism and evaporative water loss respectively). We used flow‐through respirometry to assess the energetic and hydric consequences of natural Oo infection in winter‐active pygmy rattlesnakes Sistrurus miliarius. We measured resting metabolic rate (CO₂ production rate) and total evaporative water loss rate of winter‐acclimatized S. miliarius as a function of SFD status and acute temperature (17, 25 and 32°C). We also used regression models characterizing individual variation in the thermal‐sensitivity of resting metabolic rate to predict the theoretical effects of behavioural fever on daily resting CO₂ production by free‐ranging S. miliarius with SFD in winter. Natural infection by Oo was associated with significant increases in resting metabolic rate (30%–45%) and total evaporative water loss rate (30%–40%) across all measurement temperatures. Under simulated scenarios of behavioural fever, Oo infection was predicted to increase daily resting CO₂ production rate by 58%–102%. Our results are consistent with the hypothesis that the immune response to Oo infection is energetically costly and may contribute to declining host condition. Our modelling efforts combining the cumulative effects of increased immune activity and increased body temperature on metabolism represent a novel approach in quantifying the total daily energetic cost of infection in ectothermic vertebrates undergoing behavioural fever. A free Plain Language Summary can be found within the Supporting Information of this article.

Many animals are shifting migrations in response to human activities. In particular, human-induced changes to climate and habitat (e.g., urbanization) likely facilitate animals becoming year-round residents. Because migration can be energetically expensive, shifts to sedentary behavior could minimize energetic demands incurred and any immunosuppressive effects. Residency in urban habitats could also provide abundant resources and allow sedentary animals to invest more in immunity. However, urban habitats could also expose sedentary animals to novel stressors that counter such benefits. To examine how recent shifts to residency affects physiology in ways that may shape infectious disease dynamics, we analyzed leukocyte profiles of two dark-eyed junco (Junco hyemalis) populations from southern California: the Laguna Mountain population, in which birds breed in high-elevation forests and migrate altitudinally, and the urban University of California San Diego population, which was likely established by overwintering migrants in the 1980s and has since become non-migratory. Over a two-year study of each population’s breeding season, we found no difference in the ratios of heterophils to lymphocytes between populations. However, urban residents had more leukocytes than birds from the altitudinal migrant population. A multivariate analysis suggested urban residents had fewer monocytes, but effect sizes were small. These results suggest no differences in energy demands or stressors between urban resident and altitudinal migrant populations during their breeding season. However, urban residency may confer immunological benefits through anthropogenic resources, which could have important consequences for disease dynamics..

1. Life history theory predicts that reproductive investment draws resources away from immunity, resulting in increased parasitism. However, studies of reproductive tradeoffs rarely examine multiple measures of reproduction, immunity, and parasitism. It is therefore unclear whether the immune costs of reproductive traits correlate with their resource costs, and whether increased parasitism emerges from weaker immunity.2. We examined these relationships in wild female red deer (Cervus elaphus) with variable reproductive investment and longitudinal data on mucosal antibody levels and helminth parasitism. We noninvasively collected faecal samples, counting propagules of strongyle nematodes (order: Strongylida), the common liver flukeFasciola hepaticaand the red deer tissue nematodeElaphostrongylus cervi. We also quantified both total and anti-strongyle mucosal IgA to measure general and specific immune investment.3. Contrary to our predictions, we found that gestation was associated with decreased total IgA but with no increase in parasitism. Meanwhile, the considerable resource demand of lactation had no further immune cost but was associated with higher counts of strongyle nematodes andElaphostrongylus cervi. These contrasting costs arose despite a negative correlation between antibodies and strongyle count, which implied that IgA was indicative of protective immunity.4. Our findings suggest that processes other than classical resource allocation tradeoffs are involved in mediating observed relationships between reproduction, immunity, and parasitism in wild mammals. In particular, reproduction-immunity tradeoffs may result from hormonal regulation or maternal antibody transfer, with parasitism increasing as a result of increased exposure arising from resource acquisition constraints. We advocate careful consideration of resource-independent mechanistic links and measurement of both immunity and parasitism when investigating reproductive costs.

Hosts have developed and evolved defense strategies to limit parasite damage. Hosts can reduce the damage that parasites cause by decreasing parasite fitness (resistance) or without affecting parasite fitness (tolerance). Because a parasite species can infect multiple host species, determining the effect of the parasite on these hosts and identifying host defense strategies can have important implications for multi‐host–parasite dynamics.Over 2 years, we experimentally manipulated parasitic flies (Protocalliphora sialia) in the nests of tree swallows (Tachycineta bicolor) and eastern bluebirds (Sialia sialis). We then determined the effects of the parasites on the survival of nestlings and compared defense strategies between host species. We compared resistance between host species by quantifying parasite densities (number of parasites per gram of host) and measured nestling antibody levels as a mechanism of resistance. We quantified tolerance by determining the relationship between parasite density and nestling survival and blood loss by measuring hemoglobin levels (as a proxy of blood recovery) and nestling provisioning rates (as a proxy of parental compensation for resources lost to the parasite) as potential mechanisms of tolerance.For bluebirds, parasite density was twice as high as for swallows. Both host species were tolerant to the effects of P. sialia on nestling survival at their respective parasite loads but neither species were tolerant to the blood loss to the parasite. However, swallows were more resistant to P. sialia compared to bluebirds, which was likely related to the higher antibody‐mediated immune response in swallow nestlings. Neither blood recovery nor parental compensation were mechanisms of tolerance.Overall, these results suggest that bluebirds and swallows are both tolerant of their respective parasite loads but swallows are more resistant to the parasites. These results demonstrate that different host species have evolved similar and different defenses against the same species of parasite., Host defenses to parasitic nest flies differ between tree swallows and eastern bluebirds. Both host species are tolerant to their respective parasite loads but swallows are more resistance to the parasites, which is mediated by the parasite‐binding antibody response in nestlings. Photos: Jeremy Cohen.

Using data from six wild Mojave Desert Tortoise (Gopherus agassizii (Cooper, 1861)) populations, we quantified seasonal differences in immune system measurements and microbial load in the respiratory tract, pertinent to this species’ susceptibility to upper respiratory tract disease. We quantified bacteria-killing activity of blood plasma and differential leukocyte counts to detect trends in temporal variation in immune function. We used centered log-ratio (clr) transformations of leukocyte counts and stress that such transformations are necessary for compositional data. We tested animals for the potential pathogen Pasteurella testudinis Snipes and Biberstein, 1982 with a newly created quantitative polymerase chain reaction (qPCR) assay, as well as for the known respiratory pathogens Mycoplasma agassizii Brown et al., 2001 and Mycoplasma testudineum Brown et al., 2004. We found very little disease and suggest that P. testudinis is a prevalent, commensal microbe in these Mojave Desert Tortoise populations, and its quantification may be a tool to study natural fluctuations in microbe levels in Mojave Desert Tortoise respiratory tracts. Our analyses showed that both the potential for inflammatory responses and microbe levels are highest in the spring for healthy Mojave Desert Tortoises, when lymphocyte levels are lowest. The genetic and statistical tools that we used are easily applicable to other wildlife systems and provide the necessary data to quantify species-wide trends in health and test hypotheses pertinent to host–microbe dynamics.

The many and varied effects of human‐induced environmental change have the potential to threaten animal biodiversity and species abundance. Importantly, human land use and global climate change are predicted to reduce water availability, which might have negative consequences for freshwater organisms. In this study, we tested for an effect of a shortened hydroperiod on larval growth and development, and post‐metamorphic survival and immune function in a temperate frog, Rana pipiens. Animals developing under pond drying conditions metamorphosed at a smaller size and had lower survival after metamorphosis. We found sex‐specific differences in larval period in our fastest drying treatment, with males metamorphosing more quickly than females. Individuals that developed under drying conditions also showed reduced skin swelling after phytohaemagglutinin injection, indicating a compromised immune response. We found support for trade‐offs between growth, development and post‐metamorphic immune function across hydroperiod treatments. Whole blood from animals with shorter larval periods had lower bacterial killing ability, and small‐bodied juveniles had lower antibody titres. Overall, our results indicate that a shortened hydroperiod can affect the rate of larval amphibian growth and development, and might negatively impact the condition of species that rely on freshwater for development. Our work improves understanding of the complex impacts that environmental stressors might have on the health of animal populations. A free Plain Language Summary can be found within the Supporting Information of this article.

Invasive species have become a prolific environmental issue, second only to climate change, yet many of the phenomena that facilitate invasive success are not well understood (Phillip & Shine, Proc. Roy. Soc. B, 273, 1545-1550). The combination of several generalist life-history traits, certain physiological mechanisms, and environmental conditions is thought to play a significant role in invasion success. The ability to undergo fitness trade-offs-to reallocate nutritional and energetic resources towards processes that increase reproduction, growth, and dispersal-is also thought to be an adaptive quality of many invasive species. Due to their inherent flexibility, phenotypically plastic traits in particular are often targeted for fitness reallocations. Immune function, for example, is determined by a highly plastic phenotype, which is crucial for combating a diverse array of pathogens. When active, immune function also demands extensive resources from the host. Laboratory and field studies suggest that certain aspects of the immune system are more costly than others, though, and that its components can be regulated independent of one another. In invasive species undergoing fitness trade-offs, costly innate inflammatory responses are often downregulated, while antibody-mediated responses may be enhanced. A combination of fixed physiological responses and environmentally induced trade-offs are thought to regulate the immune system, though the relationship between these facets of regulation is still an area of active research. The field of ecoimmunology, then, has emerged in effort to understand the phenomena by which individual immune regulation can drive (and be driven by) species-level ecology and evolution, and therefore be linked to invasive success (Downs et al., 2014. Integr. Compar. Biol., 54, 340-352).

The immune system is the primary barrier to parasite infection, replication, and transmission following exposure, and variation in immunity can accordingly manifest in heterogeneity in traits that govern population-level infectious disease dynamics. While much work in ecoimmunology has focused on individual-level determinants of host immune defense (e.g., reproductive status and body condition), an ongoing challenge remains to understand the broader evolutionary and ecological contexts of this variation (e.g., phylogenetic relatedness and landscape heterogeneity) and to connect these differences into epidemiological frameworks. Ultimately, such efforts could illuminate general principles about the drivers of host defense and improve predictions and control of infectious disease. Here, we highlight recent work that synthesizes the complex drivers of immunological variation across biological scales of organization and scales these within-host differences to population-level infection outcomes. Such studies note the limitations involved in making species-level comparisons of immune phenotypes, stress the importance of spatial scale for immunology research, showcase several statistical tools for translating within-host data into epidemiological parameters, and provide theoretical frameworks for linking within- and between-host scales of infection processes. Building from these studies, we highlight several promising avenues for continued work, including the application of machine learning tools and phylogenetically controlled meta-analyses to immunology data and quantifying the joint spatial and temporal dependencies in immune defense using range expansions as model systems. We also emphasize the use of organismal traits (e.g., host tolerance, competence, and resistance) as a way to interlink various scales of analysis. Such continued collaboration and disciplinary cross-talk among ecoimmunology, disease ecology, and mathematical modeling will facilitate an improved understanding of the multi-scale drivers and consequences of variation in host defense.

Background Fire strongly affects animals’ behavior, population dynamics, and environmental surroundings, which in turn are likely to affect their immune systems and exposure to pathogens. However, little work has yet been conducted on the effects of wildfires on wildlife disease. This research gap is rapidly growing in importance because wildfires are becoming globally more common and more severe, with unknown impacts on wildlife disease and unclear implications for livestock and human health in the future. Results Here, we discussed how wildfires could influence susceptibility and exposure to infection in wild animals, and the potential consequences for ecology and public health. In our framework, we outlined how habitat loss and degradation caused by fire affect animals’ immune defenses, and how behavioral and demographic responses to fire affect pathogen exposure, spread, and maintenance. We identified relative unknowns that might influence disease dynamics in unpredictable ways (e.g., through altered community composition and effects on free-living parasites). Finally, we discussed avenues for future investigations of fire-disease links. Conclusions We hope that this review will stimulate much-needed research on the role of wildfire in influencing wildlife disease, providing an important source of information on disease dynamics in the wake of future wildfires and other natural disasters, and encouraging further integration of the fields of fire and disease ecology.

Ecoimmunology conceptualizes the role of immunity in shaping life history in a natural context. Within ecoimmunology, macroimmunology is a framework that explains the effects of habitat and spatial differences on variation in immune phenotypes across populations. Within these frameworks, immune ontogeny—the development of the immune system across an individual life span—has received little attention. Here, we investigated how immune ontogeny from birth until adulthood is affected by age, sex, and developmental environment in a long-lived primate species, the bonobo. We found a progressive, significant decline of urinary neopterin levels, a marker for the cell-mediated immune response, from birth until 5 years of age in both sexes. The overall pattern of age-related neopterin changes was sex-specific, with males having higher urinary neopterin levels than females in the first 3 years of life, and females having higher levels than males between 6 and 8 years. Environmental condition (zoohoused vs. wild) did not influence neopterin levels, nor did age-related changes in neopterin levels differ between environments. Our data suggest that the post-natal development of cell-mediated immune ontogeny is sex-specific but does not show plasticity in response to environmental conditions in this long-lived primate species. This indicates that cell-mediated immune ontogeny in the bonobo follows a stereotypic and maybe a genetically determined pattern that is not affected by environmental differences in pathogen exposure and energy availability, but that sex is an important, yet often overlooked factor shaping patterns of immune ontogeny. Investigating the causes and consequences of variation in immunity throughout life is critical for our understanding of life-history evolution and strategies, mechanisms of sexual selection, and population dynamics with respect to pathogen susceptibility. A general description of sex-specific immune ontogeny as done here is a crucial step in this direction, particularly when it is considered in the context of a species’ ecology and evolutionary history. ispartof: Frontiers In Ecology And Evolution vol:9 status: published

Social status can mediate effects on the immune system, with profound consequences for individual health; nevertheless, most investigators of status-related disparities in free-ranging animals have used faecal parasite burdens to proxy immune function in the males of male-dominant species. We instead use direct measures of innate immune function (complement and natural antibodies) to examine status-related immunocompetence in both sexes of a female-dominant species. The meerkat is a unique model for such a study because it is a cooperatively breeding species in which status-related differences are extreme, evident in reproductive skew, morphology, behaviour, communication and physiology, including that dominant females naturally express the greatest total androgen (androstenedione plus testosterone) concentrations. We found that, relative to subordinates, dominant animals had reduced serum bacteria-killing abilities; also, relative to subordinate females, dominant females had reduced haemolytic complement activities. Irrespective of an individual's sex or social status, androstenedione concentrations (but not body condition, age or reproductive activity) negatively predicted concurrent immunocompetence. Thus, dominant meerkats of both sexes are immunocompromised. Moreover, in female meerkats, androstenedione perhaps acting directly or via local conversion, may exert a double-edged effect of promoting dominance and reproductive success at the cost of increased parasitism and reduced immune function. Given the prominent signalling of dominance in female meerkats, these findings may relate to the immunocompetence handicap hypothesis (ICHH); however, our data would suggest that the endocrine mechanism underlying the ICHH need not be mediated solely by testosterone and might explain trade-offs in females, as well as in males.

Recent efforts have been devoted to the link between responses to non-physical stressors and immune states in animals, mostly using human and other vertebrate models. Despite evolutionary relevance, comparatively limited work on the appraisal of predation risk and aspects of cognitive ecology and ecoimmunology has been carried out in non-chordate animals. The present study explored the capacity of holothuroid echinoderms to display an immune response to both reactive and anticipatory predatory stressors. Experimental trials and a mix of behavioural, cellular and hormonal markers were used, with a focus on coelomocytes (analogues of mammalian leukocytes), which are the main components of the echinoderm innate immunity. Findings suggest that holothuroids can not only appraise threatening cues (i.e. scent of a predator or alarm signals from injured conspecifics) but prepare themselves immunologically, presumably to cope more efficiently with potential future injuries. The responses share features with recently defined central emotional states and wane after prolonged stress in a manner akin to habituation, which are traits that have rarely been shown in non-vertebrates, and never in echinoderms. Because echinoderms sit alongside chordates in the deuterostome clade, such findings offer unique insights into the adaptive value and evolution of stress responses in animals.

Studies of the ecoimmunology of feral organisms can provide valuable insight into how host–pathogen dynamics change as organisms transition from human-managed conditions back into the wild. Honey bees (Apis mellifera Linnaeus) offer an ideal system to investigate these questions as colonies of these social insects often escape management and establish in the wild. While managed honey bee colonies have low probability of survival in the absence of disease treatments, feral colonies commonly survive in the wild, where pathogen pressures are expected to be higher due to the absence of disease treatments. Here, we investigate the role of pathogen infections [Deformed wing virus (DWV), Black queen cell virus (BQCV), and Nosema ceranae] and immune gene expression (defensin-1, hymenoptaecin, pgrp-lc, pgrp-s2, argonaute-2, vago) in the survival of feral and managed honey bee colonies. We surveyed a total of 25 pairs of feral and managed colonies over a 2-year period (2017–2018), recorded overwintering survival, and measured pathogen levels and immune gene expression using quantitative polymerase chain reaction (qPCR). Our results showed that feral colonies had higher levels of DWV but it was variable over time compared to managed colonies. Higher pathogen levels were associated with increased immune gene expression, with feral colonies showing higher expression in five out of the six examined immune genes for at least one sampling period. Further analysis revealed that differential expression of the genes hymenoptaecin and vago increased the odds of overwintering survival in managed and feral colonies. Our results revealed that feral colonies express immune genes at higher levels in response to high pathogen burdens, providing evidence for the role of feralization in altering pathogen landscapes and host immune responses.

Epidermal club cells (ECCs), along with mucus cells, are present in the skin of many fishes, particularly in the well-studied Ostariophysan family Cyprinidae. Most ECC-associated literature has focused on the potential role of ECCs as a component of chemical alarm cues released passively when a predator damages the skin of its prey, alerting nearby prey to the presence of an active predator. Because this warning system is maintained by receiver-side selection (senders are eaten), there is want of a mechanism to confer fitness benefits to the individual that invests in ECCs to explain their evolutionary origin and maintenance in this speciose group of fishes. In an attempt to understand the fitness benefits that accrue from investment in ECCs, we reviewed the phylogenetic distribution of ECCs and their histochemical properties. ECCs are found in various forms in all teleost superorders and in the chondrostei inferring either early or multiple independent origins over evolutionary time. We noted that ECCs respond to several environmental stressors/immunomodulators including parasites and pathogens, are suppressed by immunomodulators such as testosterone and cortisol, and their density covaries with food ration, demonstrating a dynamic metabolic cost to maintaining these cells. ECC density varies widely among and within fish populations, suggesting that ECCs may be a convenient tool with which to assay ecoimmunological tradeoffs between immune stress and foraging activity, reproductive state, and predator–prey interactions. Here, we review the case for ECC immune function, immune functions in fishes generally, and encourage future work describing the precise role of ECCs in the immune system and life history evolution in fishes.

With a growing number of species of conservation concern, understanding the physiological effects of routine sampling of vertebrate species remains a priority to maintain the welfare status of wildlife and ensure such activities are not counter to conservation goals. The gopher tortoise (Gopherus polyphemus) is a species of conservation concern throughout its range and is among the most frequently trapped turtles globally (for both research and conservation activities). Several studies have found equivocal results on the effects of trapping and handling on the glucocorticoid stress response. In this study, we tested how multiple physiological biomarkers (i.e. plasma lactate, corticosterone (cort), heterophil:lymphocyte ratio (HLR) and bactericidal ability (BA)) respond to four different combinations of trapping conditions in comparison to baseline reference sampling. We found that trapping and handling of gopher tortoises yielded a rapid rise in plasma lactate concentration followed by elevations of cort and stress-associated immune changes. In visibly distressed animals that were in traps for fewer than 2 hours, lactate, cort, HLR and BA were all elevated, and generally more so than animals that remained calm in traps for a similar amount of time. Animals that had been trapped and then held for a 3-hour restraint showed similar degrees of physiological alteration as those that showed outward signs of distress. This study demonstrates that trapping may yield physiological disturbances in gopher tortoises, although the intensity of this response is highly variable between individuals and the duration of such alterations remains unknown. This research emphasizes the need for continued work to refine trapping and handling processes in an effort to minimize impacts on individuals and populations.

Contaminants such as mercury are pervasive and can have immunosuppressive effects on wildlife. Impaired immunity could be important for forecasting pathogen spillover risks, as many land-use changes that generate mercury contamination also bring wildlife into close contact with humans and domestic animals. However, the interactions among contaminants, immunity, and infection are difficult to study in natural systems, and empirical tests of possible directional relationships remain rare.We capitalized on extreme mercury variation in a diverse bat community in Belize to test association among contaminants, immunity, and infection. By comparing a previous dataset of bats sampled in 2014 with new data from 2017, representing a period of rapid agricultural land conversion, we first confirmed bat species more reliant on aquatic prey had higher fur mercury. Bats in the agricultural habitat also had higher mercury in recent years. We then tested covariation between mercury and cellular immunity and determined if such relationships mediated associations between mercury and common bacterial pathogens. As bat ecology can dictate exposure to mercury and pathogens, we also assessed species-specific patterns in mercury–infection relationships.Across the bat community, individuals with higher mercury had fewer neutrophils but not lymphocytes, suggesting stronger associations with innate immunity. However, the odds of infection for hemoplasmas and Bartonella spp. were generally lowest in bats with high mercury, and relationships between mercury and immunity did not mediate infection patterns. Mercury also showed species- and clade-specific relationships with infection, being associated with especially low odds for hemoplasmas in Pteronotus mesoamericanus and Dermanura phaeotis. For Bartonella spp., mercury was associated with particularly low odds in the genus Pteronotus but high odds in the Stenodermatinae.Synthesis and application: Lower general infection risk in bats with high mercury despite weaker innate defense suggests contaminant-driven loss of pathogen habitat (i.e., anemia) or vector mortality as possible causes. Greater attention to these potential pathways could help disentangle relationships among contaminants, immunity, and infection in anthropogenic habitats and help forecast disease risks. Our results also suggest contaminants may increase infection risk in some taxa but not others, emphasizing the importance of considering surveillance and management at different phylogenetic scales.

The thymus is present in all gnathostome vertebrates and is an essential organ for the adaptive immune system via the generation of functional mature T-cells. Over the life span of mammals, the thymus undergoes morphological and functional alterations, including an age-related involution, which in humans starts in early life. Life history tradeoffs have been suggested as possible reasons for thymus involution. While in teleost fish, only a few studies have investigated alterations of thymus structure and function over different life stages, resulting in a fragmented database. Here, we investigated the thymus growth of zebrafish (Danio rerio) from early life, throughout puberty and reproductive stage, up to 1-year-old. We assessed thymus growth by histological and morphometric analyses and thymocyte numbers. Thymus function was assessed by measuring the transcripts of the thymocyte marker genes, ikaros, tcrα, and tcrδ. Additionally, we analyzed gonad maturity and tail homogenate vitellogenin concentrations to align thymus status with the status of the reproductive system. Our results showed that the zebrafish thymus, in contrast to the human thymus, grew strongly during early life and puberty but started to undergo involution when the fish reached the reproductive age. The involution was characterized by reduced thymus area and thymocyte number, altered histoarchitecture, and decreasing thymocyte marker gene transcript levels. Our findings suggest that age-related changes of the zebrafish thymus do exist and could be partly explained in terms of resource tradeoffs, but also in terms of the ontogenetically late development of a functional adaptive immune system in teleosts.

For many animals, the gut microbiome plays an essential role in immunity and digestion. However, certain animals, such as the caterpillar Manduca sexta, do not have a resident gut microbiome. Although these animals do have bacteria that pass through their gut from their natural environment, the absence of such bacteria does not reduce growth or survival. We hypothesized that M. sexta would sterilize their gut as a protective measure against secondary infection when faced with a gut infection or exposure to heat-killed bacteria in the blood (haemolymph). However, we found that gut sterilization did not occur during either type of immune challenge, i.e. bacterial numbers did not decrease. By examining the pattern of immune-related gene expression, gut pH, live bacterial counts and mass change (as a measure of sickness behaviour), we found evidence for physiological trade-offs between regulating the microbiome and defending against systemic infections. Caterpillars exposed to both gut pathogens and a systemic immune challenge had higher numbers of bacteria in their gut than caterpillars exposed to a single challenge. Following a multivariate analysis of variance, we found that the response patterns following an oral challenge, systemic challenge or dual challenge were unique. Our results suggest that the immune response for each challenge resulted in a different configuration of the immunophysiological network. We hypothesize that these different configurations represent different resolutions of physiological trade-offs based on the immune responses needed to best protect the animal against the present immune challenges.

Environmental conditions experienced by developing animals have an impact on the development and maturity of the immune system. Specifically, the diet experienced during early development influences the maintenance and function of the immune system in young and adult animals. It is well known that exposure to low-protein diets during early development are related to an attenuation of immunocompetence in adulthood. While this functional linkage has been widely studied in altricial models' mammals, it has been little explored how the nutritional history modulates the immune function in precocial animals. We evaluated the effect of dietary protein consumed during early development on the immune function and the oxidative costs in the precocial Caviomorph rodent Octodon degus, or degu. We evaluated components of the acute phase response (APR) and oxidative parameters before and after immune challenge. We found that after the immune challenge, the juveniles on the low-protein dietary treatment exhibited an attenuation of body temperature but showed higher levels of lipid peroxidation than juvenile degus on the high-protein diet. We did not find a significant effect of the interaction between diet and immune challenge on body mass, levels of inflammatory proteins, nor in the total antioxidant capacity. Our results suggest that some components of the immune function and the oxidative status in the degu can be modulated by diet during development. However, the modulation would depend on the immune variables analyzed, and the characteristics of the immune system of precocial rodents.

Billions of animals migrate between breeding and non-breeding areas worldwide. Partial migration, where both migrants and residents coexist within a population, occurs in most animal taxa, including fish, insects, birds and mammals. Partial migration has been hypothesised to be the most common form of migration and to be an evolutionary precursor to full migration. Despite extensive theoretical models about partial migration and its potential to provide insight into the ecology and evolution of migration, the physiological mechanisms that shape partial migration remain poorly understood. Here, we review current knowledge on how physiological processes mediate the causes and consequences of avian partial migration, and how they may help us understand why some individuals migrate and others remain resident. When information from birds is missing, we highlight examples from other taxa. In particular, we focus on temperature regulation, metabolic rate, immune function, oxidative stress, telomeres, and neuroendocrine and endocrine systems. We argue that these traits provide physiological pathways that regulate the ecological and behavioural causes and/or consequences of partial migration, and may provide insight into the mechanistic basis of wintering decisions. They may, thus, also help us to explain why individuals switch strategies among winters. We also highlight current gaps in our knowledge and suggest promising future research opportunities. A deeper understanding of the physiological mechanisms mediating the causes and consequences of partial migration will not only provide novel insights into the ecology and evolution of migration in general, but will also be vital to precisely modelling population trends and predicting range shifts under global change.

Historically, investigations of how organismal investments in immunity fluctuate in response to environmental and physiological changes have focused on seasonally breeding organisms that confine reproduction to seasons with relatively unchallenging environmental conditions and abundant resources. The red crossbill, Loxia curvirostra , is a songbird that can breed opportunistically if conifer seeds are abundant, on both short, cold, and long, warm days, providing an ideal system to investigate environmental and reproductive effects on immunity. In this study, we measured inter- and intra-annual variation in complement, natural antibodies, PIT54 and leucocytes in crossbills across four summers (2010–2013) and multiple seasons within 1 year (summer 2011–spring 2012). Overall, we observed substantial changes in crossbill immune investment among summers, with interannual variation driven largely by food resources, while variation across multiple seasons within a single cone year was less pronounced and lacked a dominant predictor of immune investment. However, we found weak evidence that physiological processes (e.g. reproductive condition, moult) or abiotic factors (e.g. temperature, precipitation) affect immune investment. Collectively, this study suggests that a reproductively flexible organism may be able to invest in both reproduction and survival-related processes, potentially by exploiting rich patches with abundant resources. More broadly, these results emphasize the need for more longitudinal studies of trade-offs associated with immune investment.

1.An understudied aspect of vertebrate ecoimmunology has been the relative contributions of environmental factors (E), genetic background (G) and their interaction (G × E) in shaping immune development and function. Environmental temperature is known to affect many aspects of immune function and alterations in temperature regimes have been implicated in emergent disease outbreaks, making it a critical environmental factor to study in the context of immune phenotype determinants of wild animals. 2.We assessed the relative influences of environmental temperature, genetic background and their interaction on first‐year development of innate and adaptive immune defences of captive‐born garter snakes Thamnophis elegans using a reciprocal transplant laboratory experiment. We used a full‐factorial design with snakes from two divergent life‐history ecotypes, which are known to differ in immune function in their native habitats, raised under conditions mimicking the natural thermal regime —that is, warmer and cooler— of each habitat. 3.Genetic background (ecotype) and thermal regime influenced innate and adaptive immune parameters of snakes, but in an immune‐component specific manner. We found some evidence of G × E interactions but no indication of adaptive plasticity with respect to thermal environment. At the individual level, the effects of thermal environment on resource allocation decisions varied between the fast‐ and the slow‐paced life‐history ecotypes. Under warmer conditions, which increased food consumption of individuals in both ecotypes, the former invested mostly in growth, whereas the latter invested more evenly between growth and immune development. 4.Overall, immune parameters were highly flexible, but results suggest that other environmental factors are likely more important than temperature per se in driving the ecotype differences in immunity previously documented in the snakes under field conditions. Our results also add to the understanding of investment in immune development and growth during early postnatal life under different thermal environments. Our finding of immune‐component specific patterns strongly cautions against oversimplification of the highly complex immune system in ecoimmunological studies. In conjunction, these results deepen our understanding of the degree of immunological flexibility wild animals present, information that is ever more vital in the context of rapid global environmental change. Fil: Palacios, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina. Iowa State University; Estados Unidos Fil: Gangloff, Eric J.. Iowa State University; Estados Unidos Fil: Reding, Dawn M.. Iowa State University; Estados Unidos Fil: Bronikowski, Anne M.. Iowa State University; Estados Unidos

Life-history trade-offs result from allocation of limited energetic resources to particular traits at the expense of others. When resources are scarce, some traits will take priority over others in the degree of their expression. For example, the current reproduction may be sacrificed to enhance survival. Although intuitive from an evolutionary perspective, such priorities must be based on proximate mechanisms that respond to the current conditions. The hormone leptin serves as a signal of energy availability in vertebrates, and has been proposed as a mediator of energy allocation between reproduction and traits that enhance survival, such as the immune system. However, since leptin affects reproduction and immunity in a similar way, it remains unclear which takes priority when energy availability is low. Green anole lizards (Anolis carolinensis) with increased activity, via exercise training, have a marked decrease in immune function as well as reproduction, especially when calories are restricted. We hypothesized that endurance training and calorie restriction would lower immune and reproductive function due to energy limitation, and supplemental leptin would 'rescue' either immune function or reproduction (or both) due to the hormonal signal that energetic resources are available. We found that supplementary leptin rescued immune function in calorie-restricted, trained lizards, but reproduction was not rescued in males or females. This suggests that immune function and reproduction have different sensitivities to leptin in both sexes, or that reproduction is more energy limited and takes low priority even when the signal of energy availability is present.

As infectious diseases in ectothermic vertebrates increasingly threaten wild populations, understanding how host immune systems are affected by the environment is key to understanding the process of infection. In this study, we investigated how temperature change and simulated bacterial infection (via lipopolysaccharide [LPS] injection) interacted to regulate innate immunity, as measured by bactericidal ability (BA), phagocytosis rate, and heterophil:lymphocyte ratio (HLR) in common musk turtles (Sternotherus odoratus). We found that LPS stimulated an acute immune response, as measured by an increase in BA, phagocytosis rate, and HLR. When exposed to a 5 or 10°C temperature change for 48 hr, turtles rapidly acclimated to the new temperature by adjusting their immune output. This acclimation was compensatory as seen by elevated rates of immune output in colder animals and decreased rates of immune output in warmer animals. These results indicate that while temperature change may be a constraint on some animals, S. odoratus have the ability to rapidly adjust immunity to match environmental thermal demand. This rapid ability to adjust immunity may be related to the broad geographic distribution of musk turtles. Future research should focus on how immune acclimation in ectotherms varies both intraspecifically and interspecifically across regional scales and geographic distributions.

Immune function varies with an animal’s endocrine physiology and energy reserves, as well as its abiotic and biotic environment. This context-dependency is thought to relate to adaptive trade-off resolution that varies from one context to the next; however, it is less clear how state- and environmentally-dependent differences in endocrine-immune signaling relate to survival in natural populations. We begin to address this question in a prospective study on a free-living passerine bird, the tree swallow (Tachycineta bicolor), by capitalizing upon naturally-occurring variation in ectoparasitism in 12-day old chicks. We measured body mass, hematological gene expression of the pro-inflammatory cytokine interleukin-6 (IL-6) as well as corticosterone (CORT) secretion at baseline and in response to 30 min of handling. We found that chicks with ectoparasites had smaller body mass and higher levels of IL-6 gene expression at this critical stage of post-natal growth and development. Mass and IL-6 were positively correlated, but only among parasitized chicks, suggesting that larger chicks mount stronger immune responses when necessary, i.e. in the presence of ectoparasites that are known to induce inflammation. IL-6 mRNA expression was negatively correlated with stress-induced CORT levels, suggesting that this proxy of inflammation may be co-regulated with or coordinated by glucocorticoids. More importantly, these endocrine-immune parameters predicted survival to fledging, which was positively associated with IL-6 mRNA abundance and, to a lesser degree, CORT reactivity. These results suggest a link between endocrine-immune interactions and performance in nature, and as a consequence, they shed light on the potentially adaptive, context-dependent interplay between body mass, immunity, and endocrine physiology during development.

Migration is a physiologically demanding activity. Recent studies suggest that migrating birds can improve their immune and antioxidant status during stopover, implying that variation in stopover habitat can affect migrants' health. We studied 2 species that are strongly frugivorous during fall migration, Swainson's Thrushes (Catharus ustulatus) and Gray Catbirds (Dumetella carolinensis). We asked whether birds that used shrubland dominated by exotic plants experienced differences in mass change, immune function, and antioxidant status relative to conspecifics in native-dominated shrubland during fall stopover in Michigan, USA, in 2012–2013. We found no habitat-related differences in any of the measured health parameters for Swainson's Thrushes. However, Gray Catbirds using native-dominated shrubland retained mass while those in exotic-dominated shrubland lost mass in 2013. Gray Catbirds in exotic-dominated habitat that year also had poorer immune status (elevated granulocyte:lymphocyte ratio and...

The immunocompetence of a community of free-living animals can be affected by seasonality, sex, and parasite burden. However, each of these factors is often examined independently. Recent studies have also found that dehydration can enhance aspects of immunocompetence in drought-adapted species. To explore how all of these factors interact, and their effect on the immune system in mesic-adapted species, we collected blood samples from a community of free-ranging snakes in coastal South Carolina, United States, across 2 years. We specifically examined (a) how sex and seasonality influence humoral and cellular immunocompetence and parasite burden, (b) the dynamics among hydration state, parasite burden, and immunocompetence, and (c) whether mesic-adapted species also show enhanced innate immunity with dehydration. Consistent with previous work on drought-adapted species, we found that dehydration enhances multiple aspects of humoral immunity in mesic species, and we are the first to report that dehydration also enhances aspects of cellular immunocompetence. Contrary to previous results in other squamates, sex and season did not impact immunocompetence or parasite prevalence. Our results also reveal complex interactions among parasite prevalence, immunocompetence, and hydration state demonstrating that hydration state and parasitism are two ubiquitous factors that should continue to be considered in future studies examining ecoimmunological variation.

Climate change and emerging infectious diseases are often described as the main factors associated with the worldwide amphibian population decline. In this context, rising temperatures due to global warming might act as a chronic stressor for many amphibians, leading to immunosuppression. This study aimed to characterize the thermal sensitivity of the Bullfrog's (Lithobates catesbeianus) immune response and the effect of acclimation at different temperatures on it. Plasma bacterial killing ability (BKA) and phagocytosis activity of blood leukocytes were measured at different incubation temperatures (5-40°C) in individuals kept at 28°C and 34°C. First, all individuals were held under 28°C and sampled on the 16th day. Subsequently, one group was kept at 28°, and the other one was transferred to 34°C. Both groups were sampled at 83 and 106 days of maintenance. Plasma corticosterone (CORT) and testosterone (T) were assessed to evidence thermal stress and possible endocrine correlates of immune changes over time. The incubation temperature affected BKA both on animals kept at 28°C and 34°C, with maximum values at lower temperatures (5-20°C). Phagocytosis activity was constant over the range of assay temperatures. Immune and endocrine variables decreased over time in both thermal regimes, but frogs maintained at 34°C showed lower T and immunosuppression, evidencing stress response. Therefore, exposure to high temperatures might decrease immune function in bullfrogs due to chronic stress response and by exposition to temperatures of lower performance according to the thermal sensitivity curve, which might increase vulnerability to diseases in this anuran species.

Limited resources must be partitioned among traits that enhance fitness. Although survival-related traits often trade off with reproduction, survival-related traits themselves may trade off with each other under energy limitations. Whole-organism performance and the immune system both enhance survival, yet are costly, but it is unclear how the two might trade off with each other under energy-limited conditions. Resources can be allocated to very different types of performance (e.g. aerobic endurance versus anaerobic sprinting), just as they can be allocated to different components of the immune system (e.g. innate versus acquired) to maximize survival. We forced allocation to different performance traits in green anole lizards (Anolis carolinensis) using specialized exercise training, to determine how different components of the immune system would be impacted by shifts in energy use. We measured immunocompetence in endurance-trained, sprint-trained and untrained control lizards by evaluating swelling response to phytohemagglutinin (cell-mediated immunity), antibody response to sheep red blood cells (acquired humoral immunity) and wound healing (integrated immunity). Endurance-trained lizards had reduced cell-mediated immunity, whereas sprint-trained lizards had reduced rates of wound healing. The acquired immune response was not affected by either type of training. Because each immune measure responded differently to the different types of training, our results do not support the hypothesis that simple energy limitation determines overall investment in immunity. Instead, different components of the immune system appear to be affected in ways specific to how energy is invested in performance.

Immune defense is costly to maintain and deploy, and the optimal investment into immune defense depends on risk of infection. Altitude is a natural environmental factor that is predicted to affect parasite abundance, with lower parasite abundance predicted at higher altitudes due to stronger environmental stressors, which reduce parasite transmission. Using high and low altitude populations of the Turkish blind mole-rat (TBMR) Nannospalax xanthodon, we tested for effects of altitude on constitutive innate immune defense. Field studies were performed with 32 wild animals in 2017 and 2018 from two low- and one high-altitude localities in the Central Taurus Mountains, at respective altitudes of 1010 m, 1115 m, and 2900 m above sea level. We first compared innate standing immune defense as measured by the bacteria-killing ability of blood serum. We then measured corticosterone stress hormone levels, as stressful conditions may affect immune response. Finally, we compared prevalence and intensity of gastrointestinal parasites of field-captured TBMR. We found that the bacteria-killing ability of serum is greater in the mole-rat samples from high altitude. There was no significant difference in stress (corticosterone) levels between altitude categories. Coccidian prevalence and abundance were significantly higher in 2017 than 2018 samples, but there was no significant difference in prevalence, abundance, or intensity between altitudes, or between sexes. Small sample sizes may have reduced power to detect true differences; nevertheless, this study provides support that greater standing innate immunity in high altitude animals may reflect greater investment into constitutive defense.

Integrating biological processes across scales remains a central challenge in disease ecology. Genetic variation drives differences in host immune responses, which, along with environmental factors, generates temporal and spatial infection patterns in natural populations that epidemiologists seek to predict and control. However, genetics and immunology are typically studied in model systems, whereas population-level patterns of infection status and susceptibility are uniquely observable in nature. Despite obvious causal connections, organizational scales from genes to host outcomes to population patterns are rarely linked explicitly. Here we identify two loci near genes involved in macrophage (phagocyte) activation and pathogen degradation that additively increase risk of bovine tuberculosis infection by up to ninefold in wild African buffalo. Furthermore, we observe genotype-specific variation in IL-12 production indicative of variation in macrophage activation. Here, we provide measurable differences in infection resistance at multiple scales by characterizing the genetic and inflammatory variation driving patterns of infection in a wild mammal.

Some herbivorous insects sequester chemicals from their host plants, which can serve as a defense against predators. However, sequestration can also be costly, impacting immunological responses important for other types of natural enemies, such as parasites and pathogens. These costs could also vary across herbivorous insect development, as both immune function and sequestration abilities change, although few studies have assessed variation in the cost of sequestration across life stages. The buckeye, Junonia coenia (Nymphalidae), is a specialist butterfly that sequesters iridoid glycosides from its host plants, including the introduced weed, Plantago lanceolata (Plantaginaceae). To determine the immunological costs of sequestration and how the immune response varies with host plant and across development, we reared caterpillars on a native host plant, Mimulus guttatus (Phrymaceae), which does not contain iridoid glycosides, and on P. lanceolata, which does. We assayed immune function across 3rd, 4th, and 5th instar caterpillars, estimating both hemocyte density and the ability of hemocytes to encapsulate foreign bodies by challenging the immune system with nylon filaments. For caterpillars reared on P. lanceolata, we then explored the relationships between iridoid glycoside sequestration and immune function across instars. We found that while hemocyte density tended to increase with instar regardless of host plant, caterpillars reared on P. lanceolata had lower encapsulation ability, and encapsulation decreased with increasing sequestration of iridoid glycosides, though patterns varied between instars and experimental periods. Interestingly, immune challenged caterpillars sequestered more iridoid glycosides than unchallenged caterpillars, suggesting that caterpillars responded to immune challenge by sequestering or retaining more iridoids, even though that may decrease their ability to encapsulate. These results suggest that sequestration can have important consequences for immune function across caterpillar development, and that the incorporation of novel hosts may affect defense against natural enemies.

Host competence, or how well an individual transmits pathogens, varies substantially within and among animal populations. As this variation can alter the course of epidemics and epizootics, revealing its underlying causes will help predict and control the spread of disease. One host trait that could drive heterogeneity in competence is host tolerance, which minimizes fitness losses during infection without decreasing pathogen load. In many cases, tolerance should increase competence by extending infectious periods and enabling behaviors that facilitate contact among hosts. However, we argue that the links between tolerance and competence are more varied. Specifically, the different physiological and behavioral mechanisms by which hosts achieve tolerance should have a range of effects on competence, enhancing the ability to transmit pathogens in some circumstances and impeding it in others. Because tissue-based pathology (damage) that reduces host fitness is often critical for pathogen transmission, we focus on two mechanisms that can underlie tolerance at the tissue level: damage-avoidance and damage-repair. As damage-avoidance reduces transmission-enhancing pathology, this mechanism is likely to decrease host competence and pathogen transmission. In contrast, damage-repair does not prevent transmission-relevant pathology from occurring. Rather, damage-repair provides new, healthy tissues that pathogens can exploit, likely extending the infectious period and increasing host competence. We explore these concepts through graphical models and present three disease systems in which damage-avoidance and damage-repair alter host competence in the predicted directions. Finally, we suggest that by incorporating these links, future theoretical studies could provide new insights into infectious disease dynamics and host–pathogen coevolution.

Funding was provided by Max Planck Society as well as the Deutsche Forschungsgemeinschaft (DFG) and conducted as part of the research group “Sociality and Health in Primates” (FOR2136, DE 1135/2–1 and LE1813/10–1). CC received funding from, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No 679787). Background: Ecological immunology proposes that the optimal immune defence, and the costs coming with it, vary across environments. In environments with higher pathogen load, the immune system should experience greater challenges and, therefore, investment in maintaining it should be higher. The biomarker neopterin allows monitoring of innate immune responses, and is therefore an ideal tool to investigate the effects of ecological variables on the immune system. Here, we compared urinary neopterin levels of apparently healthy chimpanzees without acute symptoms of sickness across two environments: In captivity (22 zoos) and in the wild (two populations). Results: Our results revealed that urinary neopterin levels were nearly twice as high in wild compared to captive chimpanzees, independent of chimpanzee subspecies. Conclusion: We conclude that wild chimpanzees experience more frequent immune challenges in comparison to captive individuals. Therefore, wild individuals have to allocate more energy to immune function and away from reproduction and growth. Our data indicate that the generally delayed development of wild animals in comparison to captive individuals might not only be related to lower energy intake but might result from greater energy allocations to immune function. Finally, our data highlight the importance of understanding immune costs for accurate characterization of energy budgets in animals. Publisher PDF

While the vertebrate microbiota is critical to the normal function of many host traits, hosts may expend a large amount of energy to constrain and interface with their microbiota via their immune system to avoid the high fitness costs associated with gut dysbiosis, pathobionts, and opportunistic pathogens. All jawed vertebrates share mucosal immunity dedicated to isolating the microbiota, and a breakdown of this system can result in chronic gut inflammation. In humans, chronic gut inflammation negatively affects growth and development. There is little information available on the prevalence of chronic gut inflammation in wild animals, but given that animals with different life histories emphasize different immune responses, it follows that wild animals may vary in their susceptibility to chronic gut inflammation, and most animals will experience signaling that can lead to this state. These can be top-down signals originating from sources like the central nervous system or bottom-up signals originating from changes in the gut microbiota. The sources of these signals might include stress, developmental transitions, food restriction, and dietary shifts. Here, we briefly discuss host-microbiota interactions from the perspective of life history theory and ecoimmunology, focusing on the mucosal immune system and chronic gut inflammation. We also include future directions for research and the tools necessary to investigate them.

The spread of the invasive harlequin ladybird (Harmonia axyridis) in Europe is accompanied by the decline of the native and non-invasive two-spotted ladybird (Adalia bipunctata). Here we show that microsporidia carried by H. axyridis can kill A. bipunctata following the oral uptake of spores, suggesting that their horizontal transmission via intraguild predation may help the invader to outcompete its native competitor. The native seven-spotted ladybird (Coccinella septempunctata) is thought to be less susceptible both to the spread of H. axyridis and to its microsporidia. To investigate whether the distinct levels of pathogen susceptibility in these three ladybird species are determined by their immune systems, we compared the immunity-related transcriptomes of untreated beetles and beetles challenged with suspensions of bacteria and yeast. We found that H. axyridis carries three and four times as many genes encoding antimicrobial peptides representing the attacin, coleoptericin and defensin families than C. septempunctata and A. bipunctata, respectively. Gene expression studies following the injection of bacteria and yeasts into beetles revealed that members of these three antimicrobial peptide families are also induced more strongly in H. axyridis than C. septempunctata or A. bipunctata. Our results therefore support the hypothesis that a superior immune system promotes the performance of invasive species.

Brought to Australia in 1935 to control agricultural pests (from French Guiana, via Martinique, Barbados, Jamaica, Puerto Rico and Hawai'i), repeated stepwise translocations of small numbers of founders enabled the cane toad (Rhinella marina) to escape many parasites and pathogens from its native range. However, the infective organisms that survived the journey continue to affect the dynamics of the toad in its new environment. In Australia, the native-range lungworm Rhabdias pseudosphaerocephala decreases its host's cardiac capacity, as well as growth and survival, but not rate of dispersal. The lungworm is most prevalent in long-colonised areas within the toads' Australian range, and absent from the invasion front. Several parasites and pathogens of Australian taxa have host-shifted to cane toads in Australia; for example, invasion-front toads are susceptible to spinal arthritis caused by the soil bacterium, Ochrobactrum anthropi. The pentastome Raillietiella frenata has host-shifted to toads and may thereby expand its Australian range due to the continued range expansion of the invasive toads. Spill-over and spill-back of parasites may be detrimental to other host species; however, toads may also reduce parasite loads in native taxa by acting as terminal hosts. We review the impact of the toad's parasites and pathogens on the invasive anuran's biology in Australia, as well as collateral effects of toad-borne parasites and pathogens on other host species in Australia. Both novel and co-evolved pathogens and parasites may have played significant roles in shaping the rapid evolution of immune system responses in cane toads within their invaded range., Graphical abstract Image 1, Highlights • Invasive cane toads have lost many parasites due to serial translocations. • One native lungworm (Rhabdias pseudosphaerocephala) has been retained. • Toads have also acquired novel parasites and pathogens from Australian hosts. • Toads either amplify parasite numbers or act as a parasite sink. • Differences in immune function exist between toad populations within Australia.

Studies have suggested a role for natural seasonal change to drive patterns of disease, especially within ectothermic vertebrates. In light of recent climate change, it is important to understand baseline disease resistance in a seasonal context to further understand the role that changes in seasonal weather patterns may have in increasing disease frequency. Herein we found support for the seasonal acclimation hypothesis in Gopherus polyphemus (gopher tortoise), which indicated that natural seasonal variation causes differences in baseline immune function across seasonal acclimation states. We found that an innate immune parameter, bactericidal ability (BA), was significantly elevated in the summer (P0.00001). Circulating leukocyte profiles varied significantly among seasons, with heterophils and monocytes increased (P = 0.00019 and P = 0.0001, respectively) and lymphocytes decreased (P0.00001) during winter. We assayed baseline glucocorticoid concentration (e.g., corticosterone [CORT]) across seasons and sampling conditions to test whether CORT drove the seasonal pattern in immunological acclimation. CORT was significantly lowest during winter and in animals temporarily maintained in seminatural conditions. These changes in CORT occurred independently of the immunological adjustments, suggesting that the seasonal pattern of immunity was not mediated by CORT secretion. The reduction in lymphocytes and BA and also BA during winter suggest that seasonal acclimation is likely a restraint on energetic output when temperature is low and physiological performance is thermally constrained. While these parameters were reduced in winter, the increase in heterophils and monocytes may indicate a compensatory immune adjustment to increase the number of innate phagocytic cells.

Organisms have a finite pool of resources to allocate toward multiple competing needs, such as development, reproduction, and enemy defense. Abundant resources can support investment in multiple traits simultaneously, but limited resources might promote trade-offs between fitness-related traits and immune defenses. We asked how food restriction at both larval and adult life stages of the monarch butterfly (Danaus plexippus) affected measures of immunity, fitness, and immune-fitness interactions. We experimentally infected a subset of monarchs with a specialist protozoan parasite to determine whether parasitism further affected these relationships and whether food restriction influenced the outcome of infection. Larval food restriction reduced monarch fitness measures both within the same life stage (e.g., pupal mass) as well as later in life (e.g., adult lifespan); adult food restriction further reduced adult lifespan. Larval food restriction lowered both hemocyte concentration and phenoloxidase activity at the larval stage, and the effects of larval food restriction on phenoloxidase activity persisted when immunity was sampled at the adult stage. Adult food restriction reduced only adult phenoloxidase activity but not hemocyte concentration. Parasite spore load decreased with one measure of larval immunity, but food restriction did not increase the probability of parasite infection. Across monarchs, we found a negative relationship between larval hemocyte concentration and pupal mass, and a trade-off between adult hemocyte concentration and adult life span was evident in parasitized female monarchs. Adult life span increased with phenoloxidase activity in some subsets of monarchs. Our results emphasize that food restriction can alter fitness and immunity across multiple life stages. Understanding the consequences of resource limitation for immune defense is therefore important for predicting how increasing constraints on wildlife resources will affect fitness and resistance to natural enemies.

1. Immune priming refers to improved protection of the host after a second encounter with the same parasite or pathogen. This phenomenon is similar to that of adaptive immunity in vertebrates. 2. There is evidence to suggest that this improved protection can be species/strain-specific and can protect organisms for a lifetime. These two attributes, along with a biphasic immune response, are essential characteristics of immune priming and form the basis for the effectiveness of resistance to parasites and pathogens. 3. This paper considers the effect of immune priming within and across generations, the influence of a heterologous challenge during immune priming and the importance of testing the immune response with natural pathogens. 4. The analysis presented takes into account the multifaceted nature of the invertebrate immune response. The lack of evidence suggesting that the bacterial microbiome plays a complementary role in the immune priming outcome is discussed. 5. Finally, the cost of immune priming is explored. This is a poorly investigated issue, which could help to explain why there is a paucity of evidence in support of immune priming.

Urban habitats can shape interactions between hosts and parasites by altering not only exposure rates but also within-host processes. Artificial light at night is common in urban environments, and chronic exposure can impair host immunity in ways that may increase infection. However, studies of causal links between this stressor, immunity, and infection dynamics are rare, particularly in migratory animals. Here, we experimentally tested how artificial light at night affects cellular immunity and haemosporidian parasite intensity across the annual cycle of migrant and resident subspecies of the dark-eyed junco (Junco hyemalis). We monitored an experimental group exposed to light at night and a control group under natural light/dark cycles as they passed through short days simulating early spring to longer days simulating the breeding season, followed by fall migration. Using generalized additive models, we show that artificial light at night increased inflammation, and leukocyte counts were greatest in early spring and fall. At the start of the experiment, few birds had active infections based on microscopy, but PCR revealed many birds had chronic infections. Artificial light at night increased parasitemia across the annual cycle, with strong peaks in spring and fall that were largely absent in control birds. As birds were kept in indoor aviaries to prevent vector exposure, this increased parasitemia indicates relapse of chronic infection during costly life history stages (i.e., reproduction). Although the immunological and parasitological time series were in phase for control birds, cross-correlation analyses also revealed artificial light at night desynchronized leukocyte profiles and parasitemia, which could suggest a general exaggerated inflammatory response. Our study shows how a common anthropogenic influence can shape within-host processes to affect infection dynamics.