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Vertebrate immunity is a complex system consisting of a mix of constitutive and inducible defences. Furthermore, host immunity is subject to selective pressure from a range of parasites and pathogens which can produce variation in these defences across populations. As populations evolve immune responses to parasites, they may adapt via a combination of (1) constitutive differences, (2) shared inducible responses, or (3) divergent inducible responses. Here, we leverage a powerful natural host-parasite model system (Gasterosteus aculeatus and Schistochephalus solidus) to tease apart the relative contributions of these three types of adaptations to among-population divergence in response to parasites. Gene expression analyses revealed limited evidence of significant divergence in constitutive expression of immune defence, and strong signatures of conserved inducible responses to the parasite. Furthermore, our results highlight a handful of immune-related genes which show divergent inducible responses which may contribute disproportionately to functional differences in infection success or failure. In addition to investigating variation in evolutionary adaptation to parasite selection, we also leverage this unique data set to improve understanding of cellular mechanisms underlying a putative resistance phenotype (fibrosis). Combined, our results provide a case study in evolutionary immunology showing that a very small number of genes may contribute to genotype differences in infection response.

Mining is one of the main activities that drive the economy of Brazil. Mining activity is associated with risk of contamination of environment and local fauna by metals. Amphibians have a life cycle that requires a transition between aquatic and terrestrial environments, increasing their vulnerability to metal contamination in the water and substrate. Metals are ubiquitous, with high bioaccumulative and biomagnifying potential, and may lead to immune and endocrine disruption. In this study, we analyzed two different components of the innate immune response, bacterial killing ability (BKA) and phytohemagglutinin edema (PHA), and two stress biomarkers, corticosterone plasma levels (CORT) and the neutrophil to lymphocyte ratio (N:L), of toads (Rhinella diptycha) living in places contaminated by metals. Blood samples were collected pre- and post-restraint (1h), followed by an immune challenge with PHA and tissue collection (liver, spleen, and kidneys). Toads liver metal bioaccumulation did not correlate with the immune response or stress biomarkers. Post-restraint, animals had increased CORT and reduced BKA, independently of the collection site, and these variables were not correlated with liver metal bioaccumulation. Interestingly, toads with the larger spleen (immune organ) showed increased N:L post-restraint and greater edema after the PHA challenge. Our results indicate that toads living in metal-contaminated environments responded to acute stressor, activating the hypothalamic-pituitary-interrenal axis and the immune response. Keep tracking the physiological variables of these animals and the presence of metals in the environment and tissues should provide valuable health status indicators for the population, which is vital for proposing amphibian conservation strategies in these areas.

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.

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.

With a long history of promoting pathological inflammation, eosinophils are now emerging as important regulatory cells. Yet, findings from controlled laboratory experiments so far lack translation to animals, including humans, in their natural environment. In order to appreciate the breadth of eosinophil phenotype under non‐laboratory, uncontrolled conditions, we exploit a free‐living population of the model organism Mus musculus domesticus. Eosinophils were present at significantly higher proportions in the spleen and bone marrow of wild mice compared with laboratory mice. Strikingly, the majority of eosinophils of wild mice exhibited a unique Ly6Ghi phenotype seldom described in laboratory literature. Ly6G expression correlated with activation status in spleen and bone marrow, but not peritoneal exudate cells, and is therefore likely not an activation marker per se. Intermediate Ly6G expression was transiently induced in a small proportion of eosinophils from C57BL/6 laboratory mice during acute infection with the whipworm Trichuris muris, but not during low‐dose chronic infection, which better represents parasite exposure in the wild. We conclude that the natural state of the eosinophil is not adequately reflected in the standard laboratory mouse, which compromises our attempts to dissect their functional relevance. Our findings emphasize the importance of studying the immune system in its natural context – alongside more mechanistic laboratory experiments – in order to capture the entirety of immune phenotypes and functions., Laboratory studies have ascribed eosinophils and eosinophil subsets important roles in tissue development, homeostasis and repair, yet their phenotype and function remain unclear in animals under natural conditions. Wild mice harbour a large pool of Ly6Ghi eosinophils, a phenotype rarely reported in laboratory studies and only partially explained by activation status or parasitic infections. Studying house mice in their natural environment can offer insights into environmental factors that have shaped the immune system across evolutionary timescales, complementing more traditional, mechanistic laboratory studies.

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.

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).

Investment in immune function can be costly, and life-history theory predicts trade-offs between immune function and other physiological demands. Environmental heterogeneity may constrain or change the optimal strategy and thereby alter baseline immune function (possibly mediated by stress responses). We tested several hypotheses relating variation in climatic, ecological, and social environments to chronic stress and levels of baseline innate immunity in a wild, cooperatively breeding bird, the purple-crowned fairy-wren (Malurus coronatus coronatus). From samples collected biannually over 5 yr, we quantified three indexes of constitutive innate immune function (haptoglobin/PIT54, natural antibodies, complement activity) and one index of chronic stress (heterophil-lymphocyte ratio;mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"mml:mrowmml:min/mml:mimml:mo=/mml:momml:mn513/mml:mnmml:mtext-/mml:mtextmml:mn647/mml:mn/mml:mrow/mml:math). Using an information-theoretic and multimodel inference statistical approach, we found that habitat quality and social group size did not affect any immune index, despite hypothesized links to resource abundance and parasite pressure. Rather, short-term variation in temperature and rainfall was related to immune function, while overall differences between seasons were small or absent, despite substantial seasonal variation in climate. Contrary to our expectation, we found no evidence that physiological stress mediated any effects of short-term climatic variables on immune indexes, and alternative mechanisms may be involved. Our results may be interpreted from the perspective of reactive scope models, whereby predictive homeostasis maintains standing immune function relative to long-term demands, while short-term environmental change, being less predictable, has a greater influence on baseline immune function.

The purpose of mounting an immune response is to destroy pathogens, but this response comes at a physiological cost, including the generation of oxidative damage. However, many studies on the effects of immune challenges employ a single high dose of a simulated infection, meaning that the consequences of more mild immune challenges are poorly understood. We tested whether the degree of immunological challenge in tree swallows (Tachycineta bicolor) affects oxidative physiology and body mass, and whether these metrics correlate with parasitic nest mite load. We injected 14 day old nestlings with 0, 0.01, 0.1 or 1 mg lipopolysaccharide (LPS) per kg body mass, then collected a blood sample 24 h later to quantify multiple physiological metrics, including oxidative damage (i.e. d-ROMs), circulating amounts of triglyceride and glycerol, and levels of the acute phase protein haptoglobin. After birds had fledged, we identified and counted parasitic nest mites (Dermanyssus spp. and Ornithonyssus spp.). We found that only nestlings injected with 1 mg LPS kg−1 body mass, which is a common dosage in ecoimmunological studies, lost more body mass than individuals from other treatment groups. However, every dose of LPS resulted in a commensurate increase in oxidative damage. Parasitic mite abundance had no effect on oxidative damage across treatments. The amount of oxidative damage correlated with haptoglobin levels, suggesting compensatory mechanisms to limit self-damage during an immune response. We conclude that while only the highest-intensity immune challenges resulted in costs related to body mass, even low-intensity immune challenges result in detectable increases in oxidative damage.

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

In the last decades, it is growing the idea that stress-induced immunomodulation is bimodal: with acute stress associated with enhancing effects while chronic stress with suppressive effects. However, the immune-endocrine interactions and its implications are often overlooked in ectotherms. We investigated the impact of corticosterone (CORT) treatment and short-term stressors on CORT plasma levels and the immunity of male toads (Rhinella icterica), using three distinct protocols: restraint, immune challenge (with lipopolysaccharide, LPS), and CORT transdermal application (TA). Our results showed increased CORT and neutrophil: lymphocyte ratio (NLR) regardless of the stress input (restraint, LPS challenge) or CORT TA. In the meantime, the bacterial killing ability (BKA) was not affected by any treatment, suggesting this immune parameter might be a more constitutive and robust response. Interestingly, the cellular immune response showed distinct patterns. Increased phagocytosis of blood leukocytes and phytohemagglutinin edema followed LPS and CORT TA (15 ​μg), respectively. In contrast, the phagocytosis of peritoneal leukocytes decreased after CORT TA (1 and 10 ​μg), indicating that short-term increases in CORT levels might impair local immune function. Such differences in cellular immunity might also be associated with CORT doses or the interaction between CORT and other immune mediators, such as melatonin, testosterone, and cytokines. Overall, our results highlight the immune-enhancing effects of the acute stress response and CORT TA, and the complexity of the immune-endocrine interaction in anurans. It also highlights the relevance of investigating distinct contexts for CORT increase arising from different situations, as well as diverse immune components for a better understanding of the stress-induced immunomodulation., Highlights • Restraint, LPS and exogenous CORT increased CORT plasma levels in Rhinella icterica. • Distinct acute stressors and exogenous CORT increased neutrophil: lymphocyte ratio. • LPS induced increased phagocytosis of blood cells. • Exogenous CORT increased PHA edema, and decreased phagocytosis of peritoneal cells. • BKA were sustained in all acute stress protocols and exogenous CORT treatment.

Epidemiology and life history are commonly hypothesized to influence host immune strategy, and the pairwise relationships between immune strategy and each factor have been extensively investigated. But the interaction of these two is rarely considered, despite evidence that this interaction might produce emergent effects on optimal immune strategy. Here we investigate the confluence of epidemiology and life history as it affects immune strategy through a demographically-framed model of sensitivity and specificity in parasite recognition and response. We find that variation in several different life history traits associated with both reproduction and longevity alters optimal immune strategies – but the direction and magnitude of these effects depends on how epidemiological risks vary across life. Drawing on published life history data, we also find that our predictions apply across chordate taxa. Our results shed light on the complex interactions shaping immune strategy and may prove valuable in interpreting empirical results in ecoimmunology.

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.

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.

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.

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.

Invertebrates are the protagonists of a recent paradigm shift because they now show that vertebrates are not the only group with immune memory. This review discusses the concept of immune priming, its characteristics, and differences with trained immunity and immune enhancement. We include an update of the current status of immune priming within generations in different groups of invertebrates which now include work in 5 Phyla: Ctenophora, Cnidaria, Mollusca, Nematoda, and Arthropoda. Clearly, few Phyla have been studied. We also resume and discuss the effector mechanism related to immune memory, including integrating viral elements into the genome, endoreplication, and epigenetics. The roles of other elements are incorporated, such as hemocytes, immune pathways, and metabolisms. We conclude that taking care of the experimental procedure will discern if results provide or do not support the invertebrates' immune memory and that regarding mechanisms, indeed, there are no studies on the immune memory mechanisms, this is how specificity is reached, and how and where the immune memory is stored and how is recall upon subsequent encounters. Finally, we discuss the possibility of having more than one mechanism working in different groups of invertebrates depending on the environmental conditions.

Beetles are the most diverse group of insects in Insecta which can be found in almost every habitat and environment on Earth. The possessing of the rapid and effective immune defenses is one of the important factors for their success. It is generally recognized that beetles only rely on the non-specific innate immune defense, without immunological memory, to fight against pathogens. However, there was cumulative evidence for the innate immune memory in invertebrates, including beetles, over the last decades, implying that insect innate immunity is more complex and has more features than previously thought. In beetles, it has been well documented that the specific or nonspecific enhanced immunocompetence can persist throughout development within generations and can even be transferred to the descendents in the next generation. Although insect immune priming might be shaped by epigenetic modifications and transferring effectors, mRNA and microbial signals, the solid experimental evidence to support the causal relationship between any of them and immune priming is still scarce. The combined usage of 'omics' approaches and CRISPR/Cas9 in the appropriate insect models with well-known genetic background, Tribolium castaneum and Tenebrio molitor, will help us to decipher the molecular mechanisms by which immune priming occurs in beetles in depth.

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.

The vertebrate innate immune system provides hosts with a rapid, non-specific response to a wide range of invading pathogens. However, the speed and duration of innate responses will be influenced by the co-evolutionary dynamics of specific host-pathogen combinations. Here, we show that low pathogenic avian influenza virus (LPAI) subtype H1N1 elicits a strong but extremely transient innate immune response in its main wildlife reservoir, the mallard (Anas platyrhynchos). Using a series of experimental and methodological improvements over previous studies, we followed the expression of retinoic acid inducible gene 1 (RIG-I) and myxovirus resistance gene (Mx) in mallards semi-naturally infected with low pathogenic H1N1. One day post infection, both RIG-I and Mx were significantly upregulated in all investigated tissues. By two days post infection, the expression of both genes had generally returned to basal levels, and remained so for the remainder of the experiment. This is despite the fact that birds continued to actively shed viral particles throughout the study period. We additionally show that the spleen plays a particularly active role in the innate immune response to LPAI. Waterfowl and avian influenza viruses have a long co-evolutionary history, suggesting that the mallard innate immune response has evolved to provide a minimum effective response to LPAIs such that the viral infection is brought under control while minimising the damaging effects of a sustained immune response.