Our understanding of the deterioration in immune function in old age—immunosenescence—derives principally from studies of modern human populations and laboratory animals. The generality and significance of this process for systems experiencing complex, natural infections and environmental challenges are unknown. Here, we show that late-life declines in an important immune marker of resistance to helminth parasites in wild Soay sheep predict overwinter mortality. We found senescence in circulating antibody levels against a highly prevalent nematode worm, which was associated with reduced adult survival probability, independent of changes in body weight. These findings establish a role for immunosenescence in the ecology and evolution of natural populations.
An effective immune response is expected to confer fitness benefits through improved resistance to parasites but also incur energetic costs that negatively impact fitness-related traits, such as reproduction. The fitness costs and benefits of an immune response are likely to depend on host age, sex, and levels of parasite exposure. Few studies have examined the full extent to which patterns of natural selection on immune phenotypes vary across demographic groups and environments in the wild. Here, we assessed natural selection on plasma levels of three functionally distinct isotypes (IgA, IgE, and IgG) of antibodies against a prevalent nematode parasite measured in a wild Soay sheep population over 26 years. We found little support for environment-dependent selection or reproductive costs. However, antibody levels were negatively associated with parasite egg counts and positively associated with subsequent survival, albeit in a highly age-and isotype-dependent manner. Raised levels of antiparasite IgA best predicted reduced egg counts, but this did not predict survival in lambs. In adults increased antiparasite IgG predicted reduced egg counts, and in adult females IgG levels also positively predicted overwinter survival. Our results highlight the potential importance of age-and sex-dependent selection on immune phenotypes in nature and show that patterns of selection can vary even among functionally related immune markers.
15Host-parasite interactions are powerful drivers of evolutionary and ecological dynamics in natural 16populations. Variation in immune responses to infection is likely to shape the outcome of these 17 interactions, with important consequences for the fitness of both host and parasite. However, little is 18 known about how genetic variation contributes to variation in immune responses under natural 19 conditions. Here, we examine the genetic architecture of variation in immune traits in the Soay sheep 20 of St Kilda, an unmanaged population of sheep infected with strongyle gastrointestinal nematodes. We 21 assayed IgA, IgE and IgG antibodies against the prevalent nematode Teladorsagia circumcincta in the 22 Author summary 34Host-parasite interactions are powerful drivers of evolutionary and ecological dynamics in natural 35 populations. Variation in immune responses to infection shapes the outcome of these interactions, with 36 important consequences for the ability of the host and parasite to survive and reproduce. However, little 37 is known about how much genes contribute to variation in immune responses under natural conditions. 38Our study investigates the genetic architecture of variation in three antibody types, IgA, IgE and IgG in 39 a wild population of Soay sheep on the St Kilda archipelago in North-West Scotland. Using data 40 collected over 26 years, we show that antibody levels have a heritable basis in lambs and adults and are 41 stable over lifetime of individuals. We also identify several genomic regions with large effects on 42 immune responses. Our study offers the first insights into the genetic control of immunity in a wild 43 population, which is essential to understand how immune profiles vary in challenging natural conditions 44 and how natural selection maintains genetic variation in complex immune traits. 45 46 Studies in humans and livestock have shown that variation in immune traits is often heritable; that is, a 60 significant proportion of phenotypic variance can be attributed to additive genetic effects (4-11). 61Genome-wide association studies (GWAS) in these systems have identified a number of genes of 62 relatively large effect contributing to heritable variation, most notably the major histocompatibility 63 complex (MHC) and cytokine genes (12-17). In wild populations, studies have investigated the 64 heritability of immune traits, most often in birds (18-23), with candidate gene approaches further 65 implicating MHC and cytokine regions in cases where significant associations are observed (23-28). 66However, these studies often focus on broad, non-specific immune phenotypes such as the 67 phytohaemagglutinin (PHA) response, haematocrit levels and/or parasite burden, rather than specific 68 immune responses to ecologically-relevant parasites (29-31). In addition, candidate gene studies focus 69 on a small proportion of the genome and may fail to identify previously undiscovered coding or 70 regulatory regions associated with immune trait variation (32,33). To our knowledge, there...
Much of our knowledge of the drivers of immune variation, and how these responses vary over time, comes from humans, domesticated livestock or laboratory organisms. While the genetic basis of variation in immune responses have been investigated in these systems, there is a poor understanding of how genetic variation influences immunity in natural, untreated populations living in complex environments. Here, we examine the genetic architecture of variation in immune traits in the Soay sheep of St Kilda, an unmanaged population of sheep infected with strongyle gastrointestinal nematodes. We assayed IgA, IgE and IgG antibodies against the prevalent nematode Teladorsagia circumcincta in the blood plasma of > 3,000 sheep collected over 26 years. Antibody levels were significantly heritable (h2 = 0.21 to 0.57) and highly stable over an individual’s lifespan. IgA levels were strongly associated with a region on chromosome 24 explaining 21.1% and 24.5% of heritable variation in lambs and adults, respectively. This region was adjacent to two candidate loci, Class II Major Histocompatibility Complex Transactivator (CIITA) and C-Type Lectin Domain Containing 16A (CLEC16A). Lamb IgA levels were also associated with the immunoglobulin heavy constant loci (IGH) complex, and adult IgE levels and lamb IgA and IgG levels were associated with the major histocompatibility complex (MHC). This study provides evidence of high heritability of a complex immunological trait under natural conditions and provides the first evidence from a genome-wide study that large effect genes located outside the MHC region exist for immune traits in the wild.
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