The genetics of immune and infection phenotypes in wild mice, Mus musculus domesticus

Wild animals are under constant threat from a wide range of micro- and macroparasites in their environment. Animals make immune responses against parasites, and these are important in affecting the dynamics of parasite populations. Individual animals vary in their anti-parasite immune responses. Genetic polymorphism of immune-related loci contributes to inter-individual differences in immune responses, but most of what we know in this regard comes from studies of humans or laboratory animals; there are very few such studies of wild animals naturally infected with parasites. Here we have investigated the effect of single nucleotide polymorphisms (SNPs) in immune-related loci (the major histocompatibility complex [MHC], and loci coding for cytokines and Toll-like receptors) on a wide range of immune and infection phenotypes in UK wild house mice, Mus musculus domesticus. We found strong associations between SNPs in various MHC and cytokine-coding loci on both immune measures (antibody concentration and cytokine production) and on infection phenotypes (infection with mites, worms and viruses). Our study provides a comprehensive view of how polymorphism of immune-related loci affects immune and infection phenotypes in naturally infected wild rodent populations

Short-term telomere dynamics is associated with glucocorticoid levels in wild populations of roe deer

International audienceWhile evidence that telomere length is associated with health and mortality in humans and birds is accumulating, a large body of research is currently seeking to identify factors that modulate telomere dynamics. We tested the hypothesis that high levels of glucocorticoids in individuals under environmental stress should accelerate telomere shortening in two wild populations of roe deer (Capreolus capreolus) living in different ecological contexts. From two consecutive annual sampling sessions, we found that individuals with faster rates of telomere shortening had higher concentrations of fecal glucocorticoid metabolites, suggesting a functional link between glucocorticoid levels and telomere attrition rate. This relationship was consistent for both sexes and populations. This finding paves the way for further studies of the fitness consequences of exposure to environmental stressors in wild vertebrates

Immunosenescence patterns differ between populations but not between sexes in a long-lived mammal

International audienceIn animals, physiological mechanisms underlying reproductive and actuarial senescence remain poorly understood. Immunosenescence, the decline in the ability to display an efficient immune response with increasing age, is likely to influence both reproductive and actuarial senescence through increased risk of disease. Evidence for such a link has been reported from laboratory animal models but has been poorly investigated in the wild, where variation in resource acquisitions usually drives life-history tradeoffs. We investigated immunosenescence patterns over 7 years in both sexes of two contrasting roe deer populations (Capreolus capreolus). We first measured twelve immune markers to obtain a thorough identification of innate and adaptive components of immunity and assessed, from the same individuals, the age-dependent variation observed in parasitic infections. Although the level of innate traits was maintained at old age, the functional innate immune traits declined with increasing age in one of two populations. In both populations, the production of inflammatory markers increased with advancing age. Finally, the adaptive response declined in late adulthood. The increasing parasite burden with age we reported suggests the effective existence of immunosenescence. Age-specific patterns differed between populations but not between sexes, which indicate that habitat quality could shape agedependent immune phenotype in the wild

Age-dependent associations between telomere length and environmental conditions in roe deer

Supplementary methods, tables & figure

Effet de l'âge sur les relations entre l'immunité et les traits d'histoire de vie chez un mammifère sauvage

Immunity determines an organism’s sensitivity to pathogens and parasites and thus represent a crucial function that affects survival of individuals in the wild. However, this function represents several energy costs for development and use, and in natural conditions, resources are limited. Organisms consequently face energy allocation trade-offs between costly functions such as immunity, growth or reproduction. On the long term, these allocations are supposed to have serious consequences on probability of individuals to reproduce and to survive at each age.The aim of this thesis was to describe age-related variations of immune phenotype in a wild and long-lived mammal, the roe deer (Capreolus capreolus), and to provide a better understanding of energy trade-offs between immune function and other life-history traits. This thesis was conducted in roe deer of both sexes and from two natural populations, which allow to test the influence of sex and contrasting environmental conditions on these variations.We first described that rapid growth did not impair the development of young roe deer immune phenotype (levels of innate and adaptive traits), neither on the short-term (during growth), neither on the long-term (during adulthood). We also proved that immune development of juveniles was not dependent of maternal age, but was strongly influenced by maternal body condition. In adult roe deer, we have described the precise patterns of age-related changes in ten immune traits reflecting both innate and adaptive immunity. It revealed that roe deer are subjected to profound changes in their immune profile with increasing age, i.e. an increase in the production of inflammatory markers (haptoglobin, beta-globulin) and a decrease in the adaptive response (lymphocytes). In the same individuals, the parallel increase with age of parasite load supports the idea that deer are subject to immunosenescence. Finally, we described age-related changes in leukocyte telomere length. We found no associations between telomere length and proportions of each leukocyte form (neutrophils, monocytes, lymphocytes). However, we observed that high levels of some inflammatory markers (beta- and alpha1-globulin) tend to be associated with short telomeres in immune cells. These results open many avenues for a better understanding of the physiological mechanisms underlying agingFace à la menace des pathogènes présents dans l’environnement, l’immunité représente une fonction cruciale pour la survie des organismes. Cependant, cette fonction représente divers coûts de développement et d’utilisation, et le caractère limité des ressources dans l’environnement impose des compromis d’allocation entre différentes fonctions (immunité, croissance, reproduction). Sur le long-terme, ces choix peuvent avoir de lourdes conséquences sur les probabilités de se reproduire et de survivre à chaque âge. L’objectif de cette thèse a été de décrire les variations avec l’âge du phénotype immunitaire d’un mammifère longévif, le chevreuil (Capreolus capreolus) et de mieux comprendre les compromis régissant l’allocation de ressources entre l’immunité et les autres grandes fonctions de l’organisme. Cette thèse a été menée au sein de deux populations naturelles, permettant de tester l’influence de conditions environnementales contrastées sur ces variations. Nous avons montré qu’une croissance rapide pendant les premiers mois de vie du chevreuil n’imposait pas de coûts en terme de développement du phénotype immunitaire sur la même période (niveaux des traits innés et acquis), ni sur le long-terme. Nous avons aussi montré que le développement de l’immunité des jeunes n’était pas dépendant de l’âge de leur mère, mais était fortement influencé par la condition corporelle de celle-ci. Chez les adultes, nous avons décrit les variations avec l’âge d’une dizaine de traits reflétant l’immunité innée et adaptative. Cela a permis de mettre en évidence de profondes modifications du profil immunitaire aux âges avancés, i.e. une augmentation de la production de marqueurs inflammatoires (haptoglobine, beta-globulines) et une diminution de la réponse adaptative (lymphocytes). L’augmentation parallèle avec l’âge de la charge parasitaire des individus appuie l’idée que le chevreuil est sujet à l’immunosenescence. Enfin, nous avons montré que la longueur des télomères leucocytaires varie avec l’âge. Nous n’avons pas trouvé d’associations entre la longueur des télomères et les proportions de chaque forme leucocytaire (neutrophiles, monocytes, lymphocytes). Cependant, nous avons montré que de forts niveaux de certains marqueurs inflammatoires (beta- et alpha1-globulines) semblent être associés à des télomères courts dans les cellules immunitaires. Ces résultats ouvrent de nombreuses pistes pour une meilleure compréhension des mécanismes physiologiques à la base du vieillissemen

Gut immune responses and evolution of the gut microbiome-a hypothesis.

The gut microbiome is an assemblage of microbes that have profound effects on their hosts. The composition of the microbiome is affected by bottom-up, among-taxa interactions and by top-down, host effects, which includes the host immune response. While the high-level composition of the microbiome is generally stable over time, component strains and genotypes will constantly be evolving, with both bottom-up and top-down effects acting as selection pressures, driving microbial evolution. Secretory IgA is a major feature of the gut's adaptive immune response, and a substantial proportion of gut bacteria are coated with IgA, though the effect of this on bacteria is unclear. Here we hypothesize that IgA binding to gut bacteria is a selection pressure that will drive the evolution of IgA-bound bacteria, so that they will have a different evolutionary trajectory than those bacteria not bound by IgA. We know very little about the microbiome of wild animals and even less about their gut immune responses, but it must be a priority to investigate this hypothesis to understand if and how host immune responses contribute to microbiome evolution

Maternal effects shape offspring physiological condition but do not senesce in a wild mammal

International audienc

Data from: The influence of early-life allocation to antlers on male performance during adulthood: evidence from contrasted populations of a large herbivore

1. To secure mating opportunities, males often develop and maintain conspicuous traits that are involved in intra-sexual and/or inter-sexual competition. While current models of sexual selection rely on the assumption that producing such traits is costly, quantifying the cost of allocating to secondary sexual traits remains challenging. 2. According to the principle of allocation, high energy allocation to growth or sexual traits in males should lead to reduced energy allocation to the maintenance of cellular and physiological functions, potentially causing them to age faster, with impaired survival. 3. We evaluated the short-term and delayed consequences of energy allocation to antlers early in life in two contrasted populations of roe deer, Capreolus capreolus. Although most males mate successfully for the first time in their fourth year, antlers are grown annually from the first year of life onwards. We tested the prediction that a high level of allocation to antler growth during the first two years of life should lead to lower body mass, antler size and survival during the early and late prime stages, as well as to reduced longevity overall. 4. Growing and carrying long antlers during the first years of life was not associated with any detectable cost in the late prime stage. The positive association between antler growth in early life and adult body mass instead supports that fawn antler acts as an honest signal of phenotypic quality in roe deer. 5. For a given body mass, yearling males growing longer antlers displayed impaired performance during their late prime. We also found a trend for a short-term survival cost of allocation to relative antler length during the second year of life. 6. Yearling males that grow long antlers relative to their mass might display a fast life history tactic. We argue that differential allocation to secondary sexual traits generate a diversity of individual trajectories that should impact population dynamics

Dataset_JAE-201700618

Data used in the paper "The influence of early-life allocation to antlers on male performance during adulthood: evidence from contrasted populations of a large herbivore

Does body growth impair immune function in a large herbivore?

International audienceAccording to the principle of allocation, trade-offs are inevitable when resources allocated to one biological function are no longer available for other functions. Growth, and to a lesser extent, immunity are energetically costly functions that may compete with allocation to reproductive success and survival. However, whether high allocation to growth impairs immune system development during the growing period or immune system performance during adulthood is currently unknown in wild mammals. Using three roe deer (Capreolus capreolus) populations experiencing contrasting environmental conditions, we tested for potential costs of growth on immune phenotype over both the short-term (during growth), and the long-term (during adulthood) over the course of an individuals' life. We investigated potential costs on a set of 12 immune traits that reflect both innate and adaptive responses, and compared them between sexes and populations. Although fast growth tended to be associated with low levels of some humoral traits (globulins) during the growing period and some cellular immune traits (i.e. eosinophil and neutrophil counts) during adulthood, evidence for a trade-off between growth and other immune components was limited. Unexpectedly, no detectable growth costs on immunity were found in females from the population experiencing the least favourable environment. We discuss our findings in the light of the complex interplay between resource allocation strategies among reproduction, maintenance and immunity, in relation to local environmental conditions experienced by roe deer