The major histocompatibility complex (MHC) plays an important role in infectious disease resistance. The presence of certain MHC alleles and functionally similar groups of MHC alleles (i.e., supertypes) has been associated with resistance to particular parasite species. Farmed and domesticated fish stocks are often depleted in their MHC alleles and supertype diversity, possibly as a consequence of artificial selection for desirable traits, inbreeding (loss of heterozygosity), genetic drift (loss of allelic diversity) and/or reduced parasite biodiversity. Here we quantify the effects of depletion of MHC class II genotype and supertype variation on resistance to the parasite Gyrodactylus turnbulli in guppies (Poecilia reticulata). Compared to the descendants of wild-caught guppies, ornamental fish had a significantly reduced MHC variation (i.e., the numbers of MHC alleles and supertypes per individual, and per population). In addition, ornamental fish were significantly more susceptible to G. turnbulli infections, accumulating peak intensity 10 times higher than that of their wildtype counterparts. Four out of 13 supertypes were associated with a significantly reduced parasite load, and the presence of some supertypes had a dramatic effect on the intensity of infection. Remarkably, the ornamental and wildtype fish differed in the supertypes that were associated with parasite resistance. Analysis with a genetic algorithm showed that resistance-conferring supertypes of the wildtype and ornamental fish shared two unique amino acids in the peptide-binding region of the MHC that were not found in any other alleles. These data show that the supertype demarcation captures some, but not all, of the variation in the immune function of the alleles. This study highlights the importance of managing functional MHC diversity in livestock, and suggests there might be some immunological redundancy among MHC supertypes.

Gut microbial composition plays an important role in numerous traits, including immune response. Integration of host genomic information with microbiome data is a natural step in the prediction of complex traits, although methods to optimize this are still largely unexplored. In this paper, we assess the impact of different modelling strategies on the predictive capacity for six porcine immunocompetence traits when both genotype and microbiota data are available.

Although many studies have shown that microbes can ectopically stimulate or suppress plant immune responses, the fundamental question of whether the entire preexisting microbiota is indeed required for proper development of plant immune response remains unanswered. Using a recently developed peat-based gnotobiotic plant growth system, we found that Arabidopsis grown in the absence of a natural microbiota lacked age-dependent maturation of plant immune response and were defective in several aspects of pattern-triggered immunity. Axenic plants exhibited hypersusceptibility to infection by the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and the fungal pathogen Botrytis cinerea. Microbiota-mediated immunocompetence was suppressed by rich nutrient conditions, indicating a tripartite interaction between the host, microbiota and abiotic environment. A synthetic microbiota composed of 48 culturable bacterial strains from the leaf endosphere of healthy Arabidopsis plants was able to substantially restore immunocompetence similar to plants inoculated with a soil-derived community. In contrast, a 52-member dysbiotic synthetic leaf microbiota overstimulated the immune transcriptome. Together, these results provide evidence for a causal role of a eubiotic microbiota in gating proper immunocompetence and age-dependent immunity in plants.

The observations that testosterone might be immunosuppressive, form the basis for the immunocompetence handicap hypothesis (ICHH). According to ICHH only high-quality individuals can maintain high levels of testosterone and afford the physiological cost of hormone-derived immunosuppression. The animal and human studies that attempted to support the ICHH by precisely defined impairment of immunity associated with high testosterone levels are inconclusive. Furthermore, human studies have used only selected immune functions and varying testosterone fractions. This is the first study examining the relationship between multiple innate and adaptive immunity and serum levels of free testosterone, total testosterone, DHT and DHEA in ninety-seven healthy men. Free testosterone and marginally DHT levels were positively correlated with the strength of the influenza post-vaccination response. Total testosterone and DHEA showed no immunomodulatory properties. Our findings did not support ICHH assumptions about immunosuppressive function of androgens. In the affluent society studied here, men with higher levels of free testosterone could afford to invest more in adaptive immunity. Since the hormone-immune relationship is complex and may depend on multiple factors, including access to food resources, androgens should be treated as immunomodulators rather than implicit immunosuppressants.

Gut immunocompetence involves immune, stress and regenerative processes. To investigate the determinants underlying inter-individual variation in gut immunocompetence, we perform enteric infection of 140 Drosophila lines with the entomopathogenic bacterium Pseudomonas entomophila and observe extensive variation in survival. Using genome-wide association analysis, we identify several novel immune modulators. Transcriptional profiling further shows that the intestinal molecular state differs between resistant and susceptible lines, already before infection, with one transcriptional module involving genes linked to reactive oxygen species (ROS) metabolism contributing to this difference. This genetic and molecular variation is physiologically manifested in lower ROS activity, lower susceptibility to ROS-inducing agent, faster pathogen clearance and higher stem cell activity in resistant versus susceptible lines. This study provides novel insights into the determinants underlying population-level variability in gut immunocompetence, revealing how relatively minor, but systematic genetic and transcriptional variation can mediate overt physiological differences that determine enteric infection susceptibility.

The gut microbiota influences host performance playing a relevant role in homeostasis and function of the immune system. The aim of the present work was to identify microbial signatures linked to immunity traits and to characterize the contribution of host-genome and gut microbiota to the immunocompetence in healthy pigs.

Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer and demonstrates high resistance to radiation and chemotherapy. These tumors evade immune system detection by promoting an immunosuppressive tumor microenvironment. Genetic analysis has revealed oncogenic activation of the Ras/Raf/MEK/ERK signaling pathway to be a hallmark of NSCLCs, which promotes influenza A virus (IAV) infection and replication in these cells. Thus, we aimed to unravel the oncolytic properties of IAV infection against NSCLCs in an immunocompetent model in vivo. Using Raf-BxB transgenic mice that spontaneously develop NSCLCs, we demonstrated that infection with low-pathogenic IAV leads to rapid and efficient oncolysis, eliminating 70% of the initial tumor mass. Interestingly, IAV infection of Raf-BxB mice caused a functional reversion of immunosuppressed tumor-associated lung macrophages into a M1-like pro-inflammatory active phenotype that additionally supported virus-induced oncolysis of cancer cells. Altogether, our data demonstrate for the first time in an immunocompetent in vivo model that oncolytic IAV infection is capable of restoring and redirecting immune cell functions within the tumor microenvironment of NSCLCs.

The blue mussel is a filter-feeding bivalve commonly used in ecotoxicological monitoring as a sentinel species. Due to climate change and the increase of temperature expected in marine environment, it is important to anticipate potential impacts on this species. The aim of this study was to investigate the immunocompetence of blue mussels acclimated to different temperatures and on the effects of increasing temperatures (5, 10 and 20°C). Different indices and gonad maturation stages were also determined throughout the experiments. Cell viability, phagocytosis, serum lysozyme activity and cyclooxygenase (COX) activity were evaluated as immune parameters. The cellular immunity was also evaluated after hemocytes exposure to various cadmium concentrations in vitro. The results obtained demonstrate modulation of hemocyte viability and the ability of these cells to phagocytize in absence of contaminants. After the exposure to cadmium, hemocytes showed greater viability at 5°C while maintaining a higher phagocytic competence. In addition, the lysozyme activity stayed stable at all tested temperatures, contrary to that of COX, which increased when the mussels were maintained at 20°C. The evaluation of indices demonstrated no reduction of general conditions during all the experiment despite the increase of temperature and the reduction of the digestive gland weight. Moreover, the lack of food does not affect gonad maturation and the spawning process.

The intestinal microbiota fundamentally guides the development of a normal intestinal physiology, the education, and functioning of the mucosal immune system. The Citrobacter rodentium-carrier model in germ-free (GF) mice is suitable to study the influence of selected microbes on an otherwise blunted immune response in the absence of intestinal commensals.

Genetic and functional characteristics of rice leaf endophytic actinobacterial member, Microbacterium are described. Morphotyping, multilocus sequence analysis and transmission electron microscopy indicated the species identity of the endophytic bacterium, OsEnb-ALM-D18, as Microbacterium testaceum. The endophytic Microbacterium showed probiotic solubilization of plant nutrients/minerals, produced hydrolytic enzyme/phytohormones, and showed endophytism in rice seedlings. Further, the endophytic colonization by M. testaceum OsEnb-ALM-D18 was confirmed using reporter gene coding for green fluorescence protein. Microbacterium OsEnb-ALM-D18 showed volatilome-mediated antibiosis (95.5% mycelial inhibition) on Magnaporthe oryzae. Chemical profiling of M. testaceum OsEnb-ALM-D18 volatilome revealed the abundance of 9-Octadecenoic acid, Hexadecanoic acid, 4-Methyl-2-pentanol, and 2,5-Dihydro-thiophene. Upon endobacterization of rice seedlings, M. testaceum altered shoot and root phenotype suggestive of activated defense. Over 80.0% blast disease severity reduction was observed on the susceptible rice cultivar Pusa Basmati-1 upon foliar spray with M. testaceum. qPCR-based gene expression analysis showed induction of OsCERK1, OsPAD4, OsNPR1.3, and OsFMO1 suggestive of endophytic immunocompetence against blast disease. Moreover, M. testaceum OsEnb-ALM-D18 conferred immunocompetence, and antifungal antibiosis can be the future integrated blast management strategy.

Torque Teno Virus (TTV), first discovered in 1997, is a non-pathogenic, highly prevalent virus with a notable presence in the human virome. TTV has garnered attention as a potential indicator of immunocompetence in recipients of solid organ transplants. In this review, we discuss the role of TTV as a potential marker for immunosuppression optimization, prediction of graft rejection, and as an indicator of opportunistic infections. We discuss TTV's behavior over the course of time after transplantation, TTV's implications in different immunosuppressive regimens, and potential utility in vaccinations. The review synthetizes findings from various studies depicting its potential clinical utility for future personalized patient care.

Exposure of yolk androgens can positively stimulate chick growth and competitive ability, but may negatively affect immunity. It has been hypothesized that only chicks from immunologically superior fathers can bear the cost of prenatal exposure to high androgen levels. To test this hypothesis, we paired roosters from two selection lines, one up- and one down-selected for natural antibodies (NAbs), with hens from a control line. We measured yolk testosterone and androstenedione levels, and we injected the treatment group of eggs of each female with testosterone suspended in sesame oil and the control group with sesame oil only. We then measured hatching success and growth, and characterized the humoral and cellular immune responses using three different challenges: a phyto-hemagglutinin, a lipopolysaccharide and a sheep red blood cell challenge. We found that the hatching success, body mass, initial levels of natural antibodies and the chicks' immunological responses to the three different challenges and development were affected neither by paternal immunocompetence nor by treatment. These results do not support the hypothesis that chicks from low-NAb line fathers are more sensitive to testosterone exposure during embryonic development than chicks from high-NAb line fathers.

Due to the high-quality immunogenicity of tumor-derived autophagosomes (DRibbles), we aimed to explore the antitumor ability and mechanism of DRibble-loaded dendritic cells (DRibble-DCs).

This present study was designed to evaluate the immunomodulatory activity of Konjac glucomannan (KGM) on immunosuppressed mice induced by cyclophosphamide (CTX) treatment. The mice immunodeficiency model was established by CTX. KGM was used to modulate the activities of immunosuppressive mice. It was proved that KGM could promote the proliferation of lymphocyte, thymus, and spleen indices, and alleviate the atrophy of immune organs and weight loss. Besides, in mice serum, the levels of cytokines including TNF-α, IgG, IL-2, and the contents of hemolysin were also increased after treatment with KGM. Furtherly, in nonspecific immunity, KGM could enhance natural killer (NK) cell lethality and pinocytic activity of mouse peritoneal macrophages. Therefore, all of these results revealed that KGM could improve the reduced immunity of CTX-induced mice via modulation innate immunity and adaptive immunity.

To generate peptides for presentation by major histocompatibility complex (MHC) class I molecules to T lymphocytes, the immune system of vertebrates has recruited the proteasomes, phylogenetically ancient multicatalytic high molecular weight endoproteases. We have previously shown that many of the proteolytic fragments generated by vertebrate proteasomes have structural features in common with peptides eluted from MHC class I molecules, suggesting that many MHC class I ligands are direct products of proteasomal proteolysis. Here, we report that the processing of polypeptides by proteasomes is conserved in evolution, not only among vertebrate species, but including invertebrate eukaryotes such as insects and yeast. Unexpectedly, we found that several high copy ligands of MHC class I molecules, in particular, self-ligands, are major products in digests of source polypeptides by invertebrate proteasomes. Moreover, many major dual cleavage peptides produced by invertebrate proteasomes have the length and the NH2 and COOH termini preferred by MHC class I. Thus, the ability of proteasomes to generate potentially immunocompetent peptides evolved well before the vertebrate immune system. We demonstrate with polypeptide substrates that interferon gamma induction in vivo or addition of recombinant proteasome activator 28alpha in vitro alters proteasomal proteolysis in such a way that the generation of peptides with the structural features of MHC class I ligands is optimized. However, these changes are quantitative and do not confer qualitatively novel characteristics to proteasomal proteolysis. The data suggest that proteasomes may have influenced the evolution of MHC class I molecules.

The inclusion of health-related traits, or functionally associated genetic markers, in pig breeding programs could contribute to produce more robust and disease resistant animals. The aim of the present work was to study the genetic determinism and genomic regions associated to global immunocompetence and health in a Duroc pig population. For this purpose, a set of 30 health-related traits covering immune (mainly innate), haematological, and stress parameters were measured in 432 healthy Duroc piglets aged 8 weeks. Moderate to high heritabilities were obtained for most traits and significant genetic correlations among them were observed. A genome wide association study pointed out 31 significantly associated SNPs at whole-genome level, located in six chromosomal regions on pig chromosomes SSC4, SSC6, SSC17 and SSCX, for IgG, γδ T-cells, C-reactive protein, lymphocytes phagocytic capacity, total number of lymphocytes, mean corpuscular volume and mean corpuscular haemoglobin. A total of 16 promising functionally-related candidate genes, including CRP, NFATC2, PRDX1, SLA, ST3GAL1, and VPS4A, have been proposed to explain the variation of immune and haematological traits. Our results enhance the knowledge of the genetic control of traits related with immunity and support the possibility of applying effective selection programs to improve immunocompetence in pigs.

In vivo serial passage of non-pathogenic viruses has been shown to lead to increased viral virulence, and although the precise mechanism(s) are not clear, it is known that both host and viral factors are associated with increased pathogenicity. Under- or overnutrition leads to a decreased or dysregulated immune response and can increase viral mutant spectrum diversity and virulence. The objective of this study was to identify the role of viral mutant spectra dynamics and host immunocompetence in the development of pathogenicity during in vivo passage. Because the nutritional status of the host has been shown to affect the development of viral virulence, the diet of animal model reflected two extremes of diets which exist in the global population, malnutrition and obesity. Sendai virus was serially passaged in groups of mice with differing nutritional status followed by transmission of the passaged virus to a second host species, guinea pigs. Viral population dynamics were characterized using deep sequence analysis and computational modeling. Histopathology, viral titer and cytokine assays were used to characterize viral virulence. Viral virulence increased with passage and the virulent phenotype persisted upon passage to a second host species. Additionally, nutritional status of mice during passage influenced the phenotype. Sequencing revealed the presence of several non-synonymous changes in the consensus sequence associated with passage, a majority of which occurred in the hemagglutinin-neuraminidase and polymerase genes, as well as the presence of persistent high frequency variants in the viral population. In particular, an N1124D change in the consensus sequences of the polymerase gene was detected by passage 10 in a majority of the animals. In vivo comparison of an 1124D plaque isolate to a clone with 1124N genotype indicated that 1124D was associated with increased virulence.

Little is known of how the stress response varies when animals confront seasonal life-history processes. Antioxidant defenses and damage caused by oxidative stress and their link with immunocompetence are powerful biomarkers to assess animal´s physiological stress response. The aim of this study was A) to determine redox state and variation in basal (pre-acute stress) immune function during summer, autumn and winter (spring was not assessed due to restrictions in collecting permit) in the fish-eating Myotis (Myotis vivesi; Chiroptera), and B) to determine the effect of acute stress on immunocompetence and redox state during each season. Acute stress was stimulated by restricting animal movement for 6 and 12 h. The magnitude of the cellular immune response was higher during winter whilst that of the humoral response was at its highest during summer. Humoral response increased after 6 h of movement restriction stress and returned to baseline levels after 12 h. Basal redox state was maintained throughout the year, with no significant changes in protein damage, and antioxidant activity was modulated mainly in relation to variation to environment cues, increasing during high temperatures and decreasing during windy nights. Antioxidant activity increased after the 6 h of stressful stimuli especially during summer and autumn, and to a lesser extent in early winter, but redox state did not vary. However, protein damage increased after 12 h of stress during summer. Prolonged stress when the bat is engaged in activities of high energy demand overcame its capacity to maintain homeostasis resulting in oxidative damage.

Mechanisms maintaining honesty of sexual signals are far from resolved, limiting our understanding of sexual selection and potential important parts of physiology. Carotenoid pigmented visual signals are among the most extensively studied sexual displays, but evidence regarding hypotheses on how carotenoids ensure signal honesty is mixed. Using a phylogenetically controlled meta-analysis of 357 effect sizes across 88 different species of birds, we tested two prominent hypotheses in the field: that carotenoid-dependent coloration signals i) immunocompetence and/or ii) oxidative stress state. Separate meta-analyses were performed for the relationships of trait coloration and circulating carotenoid level with different measures of immunocompetence and oxidative stress state. For immunocompetence we find that carotenoid levels (r = 0.20) and trait color intensity (r = 0.17) are significantly positively related to PHA response. Additionally we find that carotenoids are significantly positively related to antioxidant capacity (r = 0.10), but not significantly related to oxidative damage (r = -0.02). Thus our analyses provide support for both hypotheses, in that at least for some aspects of immunity and oxidative stress state the predicted correlations were found. Furthermore, we tested for differences in effect size between experimental and observational studies; a larger effect in observational studies would indicate that co-variation might not be causal. However, we detected no significant difference, suggesting that the relationships we found are causal. The overall effect sizes we report are modest and we discuss potential factors contributing to this, including differences between species. We suggest complementary mechanisms maintaining honesty rather than the involvement of carotenoids in immune function and oxidative stress and suggest experiments on how to test these.

The significant risk of disease transmission has selected for effective immune-defense strategies in insect societies. Division of labour, with individuals specialized in immunity-related tasks, strongly contributes to prevent the spread of diseases. A trade-off, however, may exist between phenotypic specialization to increase task efficiency and maintenance of plasticity to cope with variable colony demands. We investigated the extent of phenotypic specialization associated with a specific task by using allogrooming in the honeybee, Apis mellifera, where worker behaviour might lower ectoparasites load. We adopted an integrated approach to characterize the behavioural and physiological phenotype of allogroomers, by analyzing their behavior (both at individual and social network level), their immunocompetence (bacterial clearance tests) and their chemosensory specialization (proteomics of olfactory organs). We found that allogroomers have higher immune capacity compared to control bees, while they do not differ in chemosensory proteomic profiles. Behaviourally, they do not show differences in the tasks performed (other than allogrooming), while they clearly differ in connectivity within the colonial social network, having a higher centrality than control bees. This demonstrates the presence of an immune-specific physiological and social behavioural specialization in individuals involved in a social immunity related task, thus linking individual to social immunity, and it shows how phenotypes may be specialized in the task performed while maintaining an overall plasticity.