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The human immune system is capable of defending against, monitoring, and self-stabilizing various immune cells. Differentiation, proliferation, and development of these cells are regulated by biochemical signals. Moreover, biophysical signals, such as mechanical forces, have been found to affect immune cell function, thus introducing a new area of immunological research. Piezo1, a mechanically sensitive ion channel, was awarded the Nobel Prize for Physiology and Medicine in 2021. This channel is present on the surface of many cells, and when stimulated by mechanical force, it controls calcium (Ca 2+ ) inside the cells, leading to changes in downstream signals and thus regulating cell functions. Piezo1 is also expressed in various innate and adaptive immune cells and plays a major role in the immune function. In this review, we will explore the physiological functions and regulatory mechanisms of Piezo1 and its impact on innate and adaptive immunity. This may offer new insights into diagnostics and therapeutics for the prevention and treatment of diseases and surgical infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Bispecific antibodies (bsAbs) are engineered immunoglobulins that combine two different antigen-binding sites in one molecule. BsAbs can be divided into two molecular formats: IgG-like and non-IgG-like antibodies. Structural elements of each format have implications for engaging the immune system. T cell engager antibodies (TCEs) are bsAbs designed to engage T cells with target cells. TCEs can be applied not only in cancer but also in infectious disease therapy to activate T-cell responses. In this review, we focus on current literature on the design and use of bsAbs as an innovative strategy to enhance adaptive antiviral immune responses. We summarized the novel T cell-related immunotherapies with a focus on TCEs, that are developed for the treatment of chronic hepatitis B. Chronic infection with the hepatitis B virus (HBV) had a death toll of 1.1 million humans in 2022, mainly due to liver cirrhosis and hepatocellular carcinoma developing in the more than 250 million humans chronically infected. A curative treatment approach for chronic hepatitis B is lacking. Combining antiviral therapy with immune therapies activating T-cell responses is regarded as the most promising therapeutic approach to curing HBV and preventing the sequelae of chronic infection. Attracting functionally intact T cells that are not HBV-specific and, therefore, have not yet been exposed to regulatory mechanisms and activating those at the target site in the liver is a very interesting therapeutic approach that could be achieved by TCEs. Thus, TCEs redirecting T cells toward HBV-positive cells represent a promising strategy for treating chronic hepatitis B and HBV-associated hepatocellular carcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Spinal cord injury (SCI) represents a highly debilitating trauma to the central nervous system, currently lacking effective therapeutic strategies. The cascade of inflammatory responses induced by secondary damage following SCI disrupts the local immune environment at the injury site, ultimately exacerbating functional impairments post-injury. With advancing research on the gut-brain axis, evidence suggests that dysbiosis of the gut microbiota post-SCI amplifies inflammatory responses and plays a pivotal role in modulating post-injury immune-inflammatory responses. In this review article, we will explore the significant role of the gut microbiota and its metabolic products in modulating the responses of central and peripheral immune cells post-SCI, as well as their potential as therapeutic interventions for SCI treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: This study aims to investigate the effects of type 17 immune response on the proliferation of oral epithelial cells in periodontitis., Design: A time-dependent ligature induced periodontitis mouse model was utilized to explore gingival hyperplasia and the infiltration of interleukin 17A (IL-17A) positive cells. Immunohistochemistry and flow cytometry were employed to determine the localization and expression of IL-17A in the ligature induced periodontitis model. A pre-existing single-cell RNA sequencing dataset, comparing individuals affected by periodontitis with healthy counterparts, was reanalyzed to evaluate IL-17A expression levels. We examined proliferation markers, including proliferating cell nuclear antigen (PCNA), signal transducer and activator of transcription (STAT3), Yes-associated protein (YAP), and c-JUN, in the gingival and tongue epithelium of the periodontitis model. An anti-IL-17A agent was administered daily to observe proliferative changes in the oral mucosa within the periodontitis model. Cell number quantification, immunofluorescence, and western blot analyses were performed to assess the proliferative responses of human normal oral keratinocytes to IL-17A treatment in vitro., Results: The ligature induced periodontitis model exhibited a marked infiltration of IL-17A-positive cells, alongside significant increase in thickness of the gingival and tongue epithelium. IL-17A triggers the proliferation of human normal oral keratinocytes, accompanied by upregulation of PCNA, STAT3, YAP, and c-JUN. The administration of an anti-IL-17A agent attenuated the proliferation in oral mucosa., Conclusions: These findings indicate that type 17 immune response, in response to periodontitis, facilitates the proliferation of oral epithelial cells, thus highlighting its crucial role in maintaining the oral epithelial barrier., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The extensive inability of the BCG vaccine to produce long-term immune protection has not only accelerated the disease burden but also progressed towards the onset of drug resistance. In our previous study, we have reported the promising effects of Bergenin (Berg) in imparting significant protection as an adjunct immunomodulator against tuberculosis (TB). In congruence with our investigations, we delineated the impact of Berg on T cells, wherein it enhanced adaptive memory responses by modulating key transcription factors, STAT4 and Akt. We translated this finding into the vaccine model of TB and observed a notable reduction in the burden of Mycobacterium tuberculosis (M.tb) in BCG-Berg co-immunized mice as compared to BCG vaccination. Moreover, Berg, along with BCG, also aided in a heightened proinflammatory response milieu that corroborates the host protective immune response against TB. Furthermore, this response aligns with the escalated central and resident memory responses by modulating the Akt-Foxo-Stat4 axis, which plays a crucial role in enhancing the vaccine efficacy of BCG. These findings showcase the utilization of immunomodulator Berg as an immunoprophylactic agent to upgrade immunological memory, making it a more effective defender against TB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Calcium signaling stands out as the most widespread and universally used signaling system and is of utmost importance for immunity. Controlled elevations in cytosolic and organellar Ca 2+ concentrations in T cells control complex and essential effector functions including proliferation, differentiation, cytokine secretion, and cytotoxicity, among others. Additionally, disruptions in Ca 2+ regulation in T cells contribute to diverse autoimmune, inflammatory, and immunodeficiency conditions. Among the initial intracellular signals, which occurring even before T cell receptor (TCR) stimulation are highly localized, spatially and temporally restricted so-called Ca 2+ microdomains, caused by adhesion to extracellular matrix proteins (ECM proteins). The Ca 2+ microdomains present both before and within the initial seconds following TCR stimulation are likely to play a crucial role in fine-tuning the downstream activity of T cell activation and thus, shaping an adaptive immune response. In this review, the emphasis is on the recent advances of adhesion-dependent Ca 2+ microdomains (ADCM) in the absence of TCR stimulation, initial Ca 2+ microdomains evoked by TCR stimulation (TDCM), the downstream signaling processes as well as possible therapeutic targets for interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)

Infection of the respiratory tract with respiratory syncytial virus (RSV) is common and occurs repeatedly throughout life with most severe disease occurring at the extremes of age: in young infants and the elderly. Effective anti-viral therapeutics are not available and therefore prevention has been the primary strategy for reducing the disease burden. Our current understanding of respiratory mucosal cell biology and the immune response within the respiratory tract is inadequate to prevent infection caused by a pathogen like RSV that does not disseminate outside of this environment. Gaps in our understanding of the activation of innate and adaptive immunity in response to RSV and the role of age upon infection also limit improvements in the design of therapeutics and vaccines for young infants. However, advancements in structural biology have improved our ability to characterize antibodies against viral proteins and in 2023 the first vaccines for those over 60 years and pregnant women became available, potentially reducing the burden of disease. This review will examine our current understanding of the critical facets of anti-RSV immune responses in infants and young children as well as highlight areas where more research is needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type, dose (frequency/duration, intensity), and individual characteristics. Similarly, reduced availability of ambient oxygen (hypoxia) modulates immune functions depending on the hypoxic dose and the individual capacity to respond to hypoxia. How combined exercise and hypoxia (e.g., high-altitude training) sculpts immune responses is not well understood, although such combinations are becoming increasingly popular. Therefore, in this paper, we summarize the impact on immune responses of exercise and of hypoxia, both independently and together, with a focus on specialized cells in the innate and adaptive immune system. We review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia, then we discuss how they may be modulated by nutritional strategies. Mitochondrial, antioxidant, and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism, resilience, and overall immune functions by regulating the survival, differentiation, activation, and migration of immune cells. This review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system functions. Appropriate acclimatization, training, and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state., (Copyright © 2023. Production and hosting by Elsevier B.V.)

The aim of this paper is to develop and investigate a novel mathematical model of the dynamical behaviors of chronic hepatitis B virus infection. The model includes exposed infected hepatocytes, intracellular HBV DNA-containing capsids, uses a general incidence function for viral infection covering a variety of special cases available in the literature, and describes the interaction of cytotoxic T lymphocytes that kill the infected hepatocytes and the magnitude of B-cells that send antibody immune defense to neutralize free virions. Further, one time delay is incorporated to account for actual capsids production. The other time delays are used to account for maturation of capsids and free viruses. We start with the analysis of the proposed model by establishing the local and global existence, uniqueness, non-negativity and boundedness of solutions. After defined the threshold parameters, we discuss the stability properties of all possible steady state constants by using the crafty Lyapunov functionals, the LaSalle's invariance principle and linearization methods. The impacts of the three time delays on the HBV infection transmission are discussed through local and global sensitivity analysis of the basic reproduction number and of the classes of infected states. Finally, an application is provided and numerical simulations are performed to illustrate and interpret the theoretical results obtained. It is suggested that, a good strategy to eradicate or to control HBV infection within a host should concentrate on any drugs that may prolong the values of the three delays., (© 2024. The Author(s).)

Lambda interferons (IFNλs), also termed type III interferons (IFNs) or interleukins-28/29, have been in the shadow of type I IFNs for a long time. Their common induction mechanisms and signalling cascades with type I IFNs have made difficult the unwinding of their unique nonredundant functions. However, this is now changing with mounting evidence supporting a major role of IFNλs as a specialized antiviral defense system in the body, mediating protection at mucosal barrier surfaces while limiting immunopathology. Here, we review the latest progress on the complex activities of IFNλs in the respiratory tract, focusing on their multiple effects in IFNλ receptor-expressing cells, the modulation of innate and adaptive immune responses in the context of infections and respiratory diseases, and their similarities and differences with type I IFNs. We also discuss their potential in therapeutic applications and the most recent developments in that direction., Competing Interests: Declaration of Competing Interest E.A. is an inventor in a patent on interferon lambda. The remaining authors declare no competing financial interests.The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Dendritic cells (DC) play a pivotal role in the onset and progression of immunosenescence-associated diseases, serving as a link between innate and adaptive immunity. Thus, there is a need to establish reference ranges for DC subset levels in healthy adults and investigate the potential impact of age on DC subset levels and phagocytic activity. Single-platform multi-color flow cytometry was performed to assess the proportions of circulating conventional type 1 DC (cDC1), conventional type 2 DC (cDC2), and plasmacytoid DC (pDC), as well as the percentages of CD80, CD86, CD83, PD-L1, and CD32 in cDC1, cDC2, and pDC. Reference ranges were established based on age and gender, and the percentage of circulating DC subsets in different age groups was compared. In addition, circulating DC were enriched using a magnetic bead sorting kit and co-cultured with polystyrene (PS) beads, categorized by age groups, followed by the evaluation of PS bead phagocytosis using light microscopy and flow cytometry. The results indicated that the percentages of circulating cDC1, cDC2, and CD32 + cDC2 decreased with age (P < 0.05) and revealed age-related impairment in phagocytic percentage of cDC2 (P < 0.05). These findings provide a deeper understanding of the impact of age on the phenotype and phagocytic activity of DC subsets, shedding light on their role and function in immunosenescence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Macrophage receptor with collagen structure (MARCO) is a member of scavenger receptor class A (SR-A) and shares structural and functional similarities with SR-A1. In recent years, many studies have shown that MARCO can trigger an immune response and has therapeutic potential as a target for immunotherapy. Studies have shown that alterations in MARCO expression following pathogen infection cause changes in the functions of innate and adaptive immune cells, including macrophages, dendritic cells, B cells, and T cells, affecting the body's immune response to invading pathogens; thus, MARCO plays a crucial role in triggering the immune response, bridging innate and adaptive immunity, and eliminating pathogens. This paper is a comprehensive summary of the recent research on MARCO. This review focuses on the multiple functions of MARCO, including adhesion, migration, phagocytosis, and cytokine secretion with special emphasis on the complex interactions between MARCO and various types of cells involved in the immune response, as well as possible immune-related mechanisms. In summary, in this review, we discuss the structure and function of MARCO and its role in the immune response and highlight the therapeutic potential of MARCO as a target for immunotherapy. We hope that this review provides a theoretical basis for future research on MARCO., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The Arctic region's unfavorable living conditions adversely affect the spread of infectious diseases, including COVID-19, This, in turn, can also lead to increased morbidity and mortality rates in the area due to a number of factors such as climate, environment, and high prevalence rate of pre-existing health issues like diabetes, obesity, and respiratory infections. These circumstances adversely affect maintaining the level of working capability. The aim of this paper is to investigate the ratio of immunocompetent cells involved in the adaptive post-COVID-19 immune response. The research includes an immunological assessment of 29 women aged 20-40 years residing in Arkhangelsk, Russia, six months after recovering from COVID-19. The count of leukocytes in the peripheral blood and their differential were evaluated using standard methods to assess the immunological status. To delve deeper into the immunological landscape, phenotypes of lymphocytes (CD5+, CD8+, CD10+, and CD95+) were evaluated using an indirect immunoperoxidase reaction with monoclonal antibodies on dried drop lymphocyte preparations. After incubating blood with latex molecules, the activity and quantity of phagocytes were assessed using a light microscope. The neutrophil/lymphocyte ratio was found to be inverted in the female subjects under investigation. The high concentration of cytotoxic T-lymphocytes (CD8+) and lymphocytes with apoptotic receptors (CD95+) suggests a potential correlation with a concurrent reduction in the expression of the total T-cell marker (CD5+) across all cases. This association was further linked to a decrease in lymphoproliferative activity and a relative decline in phagocytic activity. These findings led us to posit that the total recovery time after COVID-19 might extend beyond six months, indicative of a prolonged impact on the body's protective capacity. Our observations prompt the hypothesis that cellular immunity plays a crucial role in determining the severity of COVID-19 infection. Specifically, individuals with initially robust phagocytic activity may be predisposed to experiencing a milder form of the infection. However, this assumption warrants further investigation and clarification in individuals with moderate and severe disease progression (Tab. 1, Ref. 17). Keywords: arctic, COVID-19, cytotoxic t-lymphocytes, apoptosis, lymphoproliferation, cellular immunity, phagocytic activity.

Introduction: Both innate and adaptive immune system undergo evolution from low to high vertebrates. Due to the limitation of conventional approaches in identifying broader spectrum of immune cells and molecules from various vertebrates, it remains unclear how immune molecules evolve among vertebrates., Objectives: Here, we utilized carry out comparative transcriptome analysis in various immune cells across seven vertebrate species., Methods: Single-cell RNA sequencing (scRNA-seq)., Results: We uncovered both conserved and species-specific profiling of gene expression in innate and adaptive immunity. Macrophages exhibited highly-diversified genes and developed sophisticated molecular signaling networks along with evolution, indicating effective and versatile functions in higher species. In contrast, B cells conservatively evolved with less differentially-expressed genes in analyzed species. Interestingly, T cells represented a dominant immune cell populations in all species and unique T cell populations were identified in zebrafish and pig. We also revealed compensatory TCR cascade components utilized by different species. Inter-species comparison of core gene programs demonstrated mouse species has the highest similarity in immune transcriptomes to human., Conclusions: Therefore, our comparative study reveals gene transcription characteristics across multiple vertebrate species during the evolution of immune system, providing insights for species-specific immunity as well as the translation of animal studies to human physiology and disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

This document is an editorial published in the journal Frontiers in Immunology. It discusses the role of adaptive immunity in atherosclerosis, a condition that contributes to acute cardiovascular events. The editorial highlights the importance of chronic inflammation in atherosclerosis and the potential for new intervention strategies. It also explores the use of new immunological techniques to study the role of the adaptive immune system in the development, progression, and regression of atherosclerosis. The document includes summaries of several research papers that investigate different aspects of adaptive immunity in atherosclerosis, including T cell and B cell responses. Overall, the editorial provides an overview of the latest findings in this field and serves as a valuable resource for researchers interested in studying adaptive immunity in atherosclerosis. [Extracted from the article]

With the deepening of people's understanding of lung cancer, the research of lung cancer immunotherapy has gradually become the focus of attention. As we all know, the treatment of many diseases relies on the rich sources, complex and varied compositions and wide range of unique biological properties of natural products. Studies have shown that natural products can exert anticancer effects by inducing tumor cell death, inhibiting tumor cell proliferation, and enhancing tumor cell autophagy. More notably, natural products can adjust and strengthen the body's immune response, which includes enhancing the function of NK cells and promoting the differentiation and proliferation of T lymphocytes. In addition, these natural products may enhance their anticancer effects by affecting inhibitory factors in the immune system, hormone levels, enzymes involved in biotransformation, and modulating other factors in the tumor microenvironment. The importance of natural products in lung cancer immunotherapy should not be underestimated. However, the specific links and correlations between natural products and lung cancer immunity are not clear enough, and further studies are urgently needed to clarify the relationship between the two. In this paper, we will focus on the correlation between natural products and lung cancer immune responses, with a view to providing new research perspectives for immunotherapy of lung cancer. [ABSTRACT FROM AUTHOR]

Postpartum breast cancer (PPBC) is a unique subset of breast cancer, accounting for nearly half of the women diagnosed during their postpartum years. Mammary gland involution is widely regarded as being a key orchestrator in the initiation and progression of PPBC due to its unique wound-healing inflammatory signature. Here, we provide dialogue suggestive that lactation may also facilitate neoplastic development as a result of sterile inflammation. Immune cells are involved in all stages of postnatal mammary development. It has been proposed that the functions of these immune cells are partially directed by mammary epithelial cells (MECs) and the cytokines they produce. This suggests that a more niche area of exploration aimed at assessing activation of innate immune pathways within MECs could provide insight into immune cell contributions to the developing mammary gland. Immune cell contribution to pubertal development and mammary gland involution has been extensively studied; however, investigations into pregnancy and lactation remain limited. During pregnancy, the mammary gland undergoes dramatic expansion to prepare for lactation. As a result, MECs are susceptible to replicative stress. During lactation, mitochondria are pushed to capacity to fulfill the high energetic demands of producing milk. This replicative and metabolic stress, if unresolved, can elicit activation of innate immune pathways within differentiating MECs. In this review, we broadly discuss postnatal mammary development and current knowledge of immune cell contribution to each developmental stage, while also emphasizing a more unique area of study that will be beneficial in the discovery of novel therapeutic biomarkers of PPBC. [ABSTRACT FROM AUTHOR]

B cells and the antibodies they produce are critical in host defense against pathogens and contribute to various immune-mediated diseases. B cells responding to activating signals in vitro release extracellular vesicles (EV) that carry surface antibodies, yet B cell production of EVs that express antibodies and their function in vivo is incompletely understood. Using transgenic mice expressing the Cre recombinase in B cells switching to IgG1 to induce expression of fusion proteins between emerald green fluorescent protein (emGFP) and the EV tetraspanin CD63 as a model, we identify emGFP expression in B cells responding to foreign antigen in vivo and characterize the emGFP+ EVs they release. Our data suggests that emGFP+ germinal center B cells undergoing immunoglobulin class switching to express IgG and their progeny memory B cells and plasma cells, also emGFP+, are sources of circulating antigen-specific IgG+ EVs. Furthermore, using a mouse model of influenza virus infection, we find that IgG+ EVs specific for the influenza hemagglutinin antigen protect against virus infection. In addition, crossing the B cell Cre driver EV reporter mice onto the Nba2 lupus-prone strain revealed increased circulating emGFP+ EVs that expressed surface IgG against nuclear antigens linked to autoimmunity. These data identify EVs loaded with antibodies as a novel route for antibody secretion in B cells that contribute to adaptive immune responses, with important implications for different functions of IgG+ EVs in infection and autoimmunity. [ABSTRACT FROM AUTHOR]

Through immune memory, infections have a lasting effect on the host. While memory cells enable accelerated and enhanced responses upon rechallenge with the same pathogen, their impact on susceptibility to unrelated diseases is unclear. We identify a subset of memory T helper 1 (Th1) cells termed innate acting memory T (TIA) cells that originate from a viral infection and produce IFN-γ with innate kinetics upon heterologous challenge in vivo. Activation of memory TIA cells is induced in response to IL-12 in combination with IL-18 or IL-33 but is TCR independent. Rapid IFN-γ production by memory TIA cells is protective in subsequent heterologous challenge with the bacterial pathogen Legionella pneumophila. In contrast, antigen-independent reactivation of CD4+ memory TIA cells accelerates disease onset in an autoimmune model of multiple sclerosis. Our findings demonstrate that memory Th1 cells can acquire additional TCR-independent functionality to mount rapid, innate-like responses that modulate susceptibility to heterologous challenges. [ABSTRACT FROM AUTHOR]

Our ability to fight pathogens relies on major histocompatibility complex class I (MHC-I) molecules presenting diverse antigens on the surface of diseased cells. The transporter associated with antigen processing (TAP) transports nearly the entire repertoire of antigenic peptides into the endoplasmic reticulum for MHC-I loading. How TAP transports peptides specific for MHC-I is unclear. In this study, we used cryo-EM to determine a series of structures of human TAP, both in the absence and presence of peptides with various sequences and lengths. The structures revealed that peptides of eight or nine residues in length bind in a similarly extended conformation, despite having little sequence overlap. We also identified two peptide-anchoring pockets on either side of the transmembrane cavity, each engaging one end of a peptide with primarily main chain atoms. Occupation of both pockets results in a global conformational change in TAP, bringing the two halves of the transporter closer together to prime it for isomerization and ATP hydrolysis. Shorter peptides are able to bind to each pocket separately but are not long enough to bridge the cavity to bind to both simultaneously. Mutations that disrupt hydrogen bonds with the N and C termini of peptides almost abolish MHC-I surface expression. Our findings reveal that TAP functions as a molecular caliper that selects peptides according to length rather than sequence, providing antigen diversity for MHC-I presentation. [ABSTRACT FROM AUTHOR]

Molecular timing mechanisms known as circadian clocks drive endogenous 24-h rhythmicity in most physiological functions, including innate and adaptive immunity. Consequently, the response to immune challenge such as vaccination might depend on the time of day of exposure. This study assessed whether the time of day of vaccination (TODV) is associated with the subsequent immune and clinical response by conducting a systematic review of previous studies. The Cochrane Library, PubMed, Google, Medline, and Embase were searched for studies that reported TODV and immune and clinical outcomes, yielding 3114 studies, 23 of which met the inclusion criteria. The global severe acute respiratory syndrome coronavirus 2 vaccination program facilitated investigation of TODV and almost half of the studies included reported data collected during the COVID-19 pandemic. There was considerable heterogeneity in the demography of participants and type of vaccine, and most studies were biased by failure to account for immune status prior to vaccination, self-selection of vaccination time, or confounding factors such as sleep, chronotype, and shiftwork. The optimum TODV was concluded to be afternoon (5 studies), morning (5 studies), morning and afternoon (1 study), midday (1 study), and morning or late afternoon (1 study), with the remaining 10 studies reporting no effect. Further research is required to understand the relationship between TODV and subsequent immune outcome and whether any clinical benefit outweighs the potential effect of this intervention on vaccine uptake. [ABSTRACT FROM AUTHOR]

Introduction: Antibodies against the SARS-CoV-2 spike protein are a critical immune determinant for protection against the virus. While virus neutralization is a key function of spike-specific antibodies, antibodies also mediate Fcdependent activities that can play a role in protection or pathogenesis. Methods: This study characterized serum antibody responses elicited after two doses of heterologous adenovirus-vectored (Ad26/Ad5) vaccines. Results: Vaccine-induced antibody binding titers and Fc-mediated functions decreased over six months, while neutralization titers remained stable. Comparison of antibody isotypes elicited after Ad26/Ad5 vs. LNP-mRNA vaccination and after infection showed that anti-spike IgG1 were dominant and produced to high levels in all groups. The Ad26/Ad5 vaccines also induced IgG4 but not IgG2 and IgG3, whereas the LNP-mRNA vaccines elicited a full Ig spectrum (IgM, IgG1-4, IgA1-2). Convalescent COVID-19 patients had mainly IgM and IgA1 alongside IgG1. Despite these differences, the neutralization potencies against early variants were similar. However, both vaccine groups had antibodies with greater Fc potencies of binding complement and Fcg receptors than the COVID-19 group. The Ad26/Ad5 group also displayed a greater potency of RBD-specific antibody-mediated cellular phagocytosis. Discussion: Antibodies with distinctive quality were induced by different vaccines and infection. The data imply the utility of different vaccine platforms to elicit antibody responses with fine-tuned Fc activities. [ABSTRACT FROM AUTHOR]

Background: Protective immunity against intestinal helminths requires induction of robust type-2 immunity orchestrated by various cellular and soluble effectors which promote goblet cell hyperplasia, mucus production, epithelial proliferation, and smooth muscle contractions to expel worms and reestablish immune homeostasis. Conversely, defects in type-2 immunity result in ineffective helminth clearance, persistent infection, and inflammation. Macrophages are highly plastic cells that acquire an alternatively activated state during helminth infection, but they were previously shown to be dispensable for resistance to Trichuris muris infection. Methods: We use the in vivo mouse model A20myel-KO, characterized by the deletion of the potent anti-inflammatory factor A20 (TNFAIP3) specifically in the myeloid cells, the excessive type-1 cytokine production, and the development of spontaneous arthritis. We infect A20myel-KO mice with the gastrointestinal helminth Trichuris muris and we analyzed the innate and adaptive responses. We performed RNA sequencing on sorted myeloid cells to investigate the role of A20 on macrophage polarization and type-2 immunity. Moreover, we assess in A20myel-KO mice the pharmacological inhibition of type-1 cytokine pathways on helminth clearance and the infection with Salmonella typhimurium. Results: We show that proper macrophage polarization is essential for helminth clearance, and we identify A20 as an essential myeloid factor for the induction of type-2 immune responses against Trichuris muris. A20myel-KO mice are characterized by persistent Trichuris muris infection and intestinal inflammation. Myeloid A20 deficiency induces strong classical macrophage polarization which impedes anti-helminth type-2 immune activation; however, it promotes detrimental Th1/Th17 responses. Antibody-mediated neutralization of the type-1 cytokines IFN-γ, IL-18, and IL-12 prevents myeloid-orchestrated Th1 polarization and re-establishes type-2-mediated protective immunity against T. muris in A20myel-KO mice. In contrast, the strong Th1-biased immunity in A20myel-KO mice offers protection against Salmonella typhimurium infection. Conclusions: We hereby identify A20 as a critical myeloid factor for correct macrophage polarization and appropriate adaptive mucosal immunity in response to helminth and enteric bacterial infection. [ABSTRACT FROM AUTHOR]

The optimal immune response eliminates invading pathogens, restoring immune equilibrium without inflicting undue harm to the host. However, when a cascade of immunological reactions is triggered, the immune response can sometimes go into overdrive, potentially leading to harmful long-term effects or even death. The immune system is triggered mostly by infections, allergens, or medical interventions such as vaccination. This review examines how these immune triggers differ and why certain infections may dysregulate immune homeostasis, leading to inflammatory or allergic pathology and exacerbation of pre-existing conditions. However, many vaccines generate an optimal immune response and protect against the consequences of pathogen-induced immunological aggressiveness, and from a small number of unrelated pathogens and autoimmune diseases. Here, we propose an "immuno-wave" model describing a vaccine-induced "Goldilocks immunity", which leaves fine imprints of both pro-inflammatory and anti-inflammatory milieus, derived from both the innate and the adaptive arms of the immune system, in the body. The resulting balanced, 'quiet alert' state of the immune system may provide a jump-start in the defense against pathogens and any associated pathological inflammatory or allergic responses, allowing vaccines to go above and beyond their call of duty. In closing, we recommend formally investigating and reaping many of the secondary benefits of vaccines with appropriate clinical studies. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection can trigger cytokine storm in some patients, which characterized by an excessive production of cytokines and chemical mediators. This hyperactive immune response may cause significant tissue damage and multiple organ failure (MOF). The severity of COVID-19 correlates with the intensity of cytokine storm, involving elements such as IFN, NF-κB, IL-6, HMGB1, etc. It is imperative to rapidly engage adaptive immunity to effectively control the disease progression. CD4+ T cells facilitate an immune response by improving B cells in the production of neutralizing antibodies and activating CD8+ T cells, which are instrumental in eradicating virus-infected cells. Meanwhile, antibodies from B cells can neutralize virus, obstructing further infection of host cells. In individuals who have recovered from the disease, virus-specific antibodies and memory T cells were observed, which could confer a level of protection, reducing the likelihood of re-infection or attenuating severity. This paper discussed the roles of macrophages, IFN, IL-6 and HMGB1 in cytokine release syndrome (CRS), the intricacies of adaptive immunity, and the persistence of immune memory, all of which are critical for the prevention and therapeutic strategies against COVID-19.

This document is an editorial published in the journal Frontiers in Immunology. It discusses the importance of prognostic and predictive factors in autoimmune connective tissue disorders. These disorders are complex and can have variable disease courses, making it difficult to predict outcomes and determine the most effective treatments. The editorial highlights the need for biomarkers that can help predict disease severity and long-term survival. The document also mentions several research articles that were published on this topic, covering various aspects of autoimmune connective tissue disorders and their prognostic factors. [Extracted from the article]

Currently, vaccine development against different respiratory diseases is at its peak. It is of utmost importance to find suitajble adjuvants that can increase the potency of the vaccine candidates. This study aimed to determine the systemic and splenic immune mechanisms in mice models induced by anionic and cationic lipid adjuvants in the presence of the vaccine-candidate influenza antigen hemagglutinin (HA). In the presence of the HA antigen, the cationic adjuvant (N3) increased conventional dendritic cell 1 (cDC1) abundance with enhanced MHCI and CD80-CD86 costimulatory marker expression, and significantly higher CD8T and Th17 populations with enhanced interferon-gamma (IFNγ) expression in CD8T and CD4T populations. Conversely, the anionic adjuvant (L3) increased the cDC2 population percentage with significantly higher MHCII and DEC205 expression, along with an increase in the CD4T and regulatory T cell populations. The L3-treated group also exhibited higher percentages of activated B and plasma cell populations with significantly higher antigen-specific IgG and IgA titer and virus neutralization potential. While the anionic adjuvant induced significantly higher humoral responses than the cationic adjuvant, the latter influenced a significantly higher Th1/Th17 response. For customized vaccine development, it is beneficial to have alternative adjuvants that can generate differential immune responses with the same vaccine candidate antigen. This study will aid the selection of adjuvants based on their charges to improve specific immune response arms in the future development of vaccine formulation. [ABSTRACT FROM AUTHOR]

Background: Vaccination against COVID-19 is highly effective in preventing severe disease and hospitalization, but primary COVID mRNA vaccination schedules often differed from those recommended by the manufacturers due to supply chain issues. We investigated the impact of delaying the second dose on antibody responses to COVID mRNA-vaccines in a prospective cohort of health-care workers in Quebec. Methods: We recruited participants from the McGill University Health Centre who provided serum or participant-collected dried blood samples (DBS) at 28- days, 3 months, and 6 months post-second dose and at 28-days after a third dose. IgG antibodies to SARS-CoV2 spike (S), the receptor-binding domain (RBD), nucleocapsid (N) and neutralizing antibodies to the ancestral strain were assessed by enzyme-linked immunosorbent assay (ELISA). We examined associations between long (≤89 days) versus short (<89 days) between-dose intervals and antibody response through multivariable mixed-effects models adjusted for age, sex, prior covid infection status, time since vaccine dose, and assay batch. Findings: The cohort included 328 participants who received up to three vaccine doses (>80% Pfizer-BioNTech). Weighted averages of the serum (n=744) and DBS (n=216) cohort results from the multivariable models showed that IgG anti-S was 31% higher (95% CI: 12% to 53%) and IgG anti-RBD was 37% higher (95% CI: 14% to 65%) in the long vs. short interval participants, across all time points. Interpretation: Our study indicates that extending the covid primary series between-dose interval beyond 89 days (approximately 3 months) provides stronger antibody responses than intervals less than 89 days. Our demonstration of a more robust antibody response with a longer between dose interval is reassuring as logistical and supply challenges are navigated in low-resource settings. [ABSTRACT FROM AUTHOR]

Babesia microti (B. microti) is a tick-transmitted protozoan parasite that invades red blood cells. It is the primary cause of human babesiosis in the US. The severity of babesiosis caused by B. microti infection can range from asymptomatic to fatal. Risk factors for severe disease include general immune suppression, advanced age (>50) and lack of a spleen. However, severe disease can occur in the absence of any known risk factors. The degree to which tick-transmitted B. microti infection confers protection from subsequent exposure is largely unexplored. This is an important question as both the prevalence and geographic range of tick-transmitted B. microti infection continues to increase and individuals in endemic regions may have multiple exposures over their lifetime. In the current study we used a mouse model to evaluate the degree to which primary infection with B. microti protected against secondary challenge with the same parasite strain. We show that CD4 T cells, and to a lesser extent B cells, contribute to protection. However, mice exhibited significant protection from secondary parasite challenge even in the absence of either CD4 T cells or B cells. The protection mediated by CD4 T cells did not depend on their production of IFN-γ as mice with a targeted gene deletion for the IFN-γ receptor remained fully protected against secondary challenge. Other factors including inducible nitric oxide synthase (iNOS) and the adaptor protein MyD88, important for toll-like receptors, IL-18 and IL-1 signaling, were not important for protection against primary or secondary challenge with B. microti. Thus, our study shows that resolution of primary infection with B. microti results in robust protection against secondary challenge with parasites, at least in the short term. Further studies are needed to evaluate the length of protection and the degree to which protection is impacted by parasite heterogeneity. Although we show an important role for CD4 T cells in protection against secondary challenge, our results suggest that no single aspect of the immune system is solely responsible for adequate protection against secondary challenge with B. microti. [ABSTRACT FROM AUTHOR]

The larval waste, exoskeleton shedding, and leftover feed components of the black soldier fly and its larvae make up the by-product known as frass. In this study, we subjected channel catfish (Ictalurus punctatus) to a 10-week feeding trial to assess how different dietary amounts of frass inclusion would affect both systemic and mucosal tissue gene expression, especially in regard to growth and immunerelated genes. Fish were divided in quadruplicate aquaria, and five experimental diets comprising 0, 50, 100, 200, and 300 g of frass per kilogram of feed were fed twice daily. At the end of the trial, liver, head kidney, gill, and intestine samples were collected for gene expression analyses. First, liver and intestine samples from fish fed with a no frass inclusion diet (control), low-frass (50 g/kg) inclusion diet, or a high-frass (300 g/kg) inclusion diet were subjected to Illumina RNA sequencing to determine global differential gene expression among diet groups. Differentially expressed genes (DEGs) included the upregulation of growth-related genes such as glucose-6-phosphatase and myostatin, as well as innate immune receptors and effector molecules such as toll-like receptor 5, apolipoprotein A1, C-type lectin, and lysozyme. Based on the initial screenings of low/high frass using RNA sequencing, a more thorough evaluation of immune gene expression of all tissues sampled, and all levels of frass inclusion, was further conducted. Using targeted quantitative PCR panels for both innate and adaptive immune genes from channel catfish, differential expression of genes was identified, which included innate receptors (TLR1, TLR5, TLR9, and TLR20A), proinflammatory cytokines (IL-1ß type a, IL-1ß type b, IL-17, IFN-1, and TNFa), chemokines (CFC3 and CFD), and hepcidin in both systemic (liver and head kidney) and mucosal (gill and intestine) tissues. Overall, frass from black soldier fly larvae inclusion in formulated diets was found to alter global gene expression and activate innate and adaptive immunity in channel catfish, which has the potential to support disease resistance in this species in addition to demonstrated growth benefits. [ABSTRACT FROM AUTHOR]

This article, published in Frontiers in Immunology, discusses the role of adipose tissue and resident immune cells in infections. Adipose tissue can influence immune responses to infection by regulating the expression of certain molecules. Immune cells within adipose tissue can also impact the overall metabolism of the body. The article also explores the idea that adipose tissue may serve as a safe haven for parasites, allowing them to establish chronic infections. The authors emphasize the need for further research to better understand the interactions between parasites and adipose tissue, which could lead to new therapeutic approaches. [Extracted from the article]