The early developmental environment has a profound influence on an individual's life history trajectory and parents have tremendous influence over this environment. Despite the wealth of research demonstrating that incubation temperature affects a suite of traits important to fitness in reptiles, we are only now discovering that nest temperatures are a defining component of the avian developmental environment. Aspects of the nest environment may be an important and overlooked maternal effect in birds as nearly all birds physically incubate their eggs, thus providing a clear link between parental behavior and the developmental environment of the avian embryo. My research used an interdisciplinary approach, uniting concepts from life history theory, bioenergetics. immunology, and physiological ecology to investigate the importance of incubation temperature to avian phenotype. I found that incubation temperature affects a suite of traits important for future development, survival and reproduction in a species of birds. Using a population of wood ducks (Aix sponsa) that has been the subject of long term studies I investigated the effects of incubation temperature on embryonic developmental patterns and energy expenditure, and body size and condition, stress endocrinology, thermoregulatory performance, and immunocompetence in hatchling wood ducks. In all experiments freshly laid wood duck eggs were collected from nest boxes located in SC, transported to Virginia Tech and incubated at one of three temperatures (35.0, 35.9, 37.0Ë C) that fell within the range of naturally-incubated wood duck nest temperatures. I found that less than 1Ë C differences in incubation temperature affected duckling growth and body condition, stress endocrinology, immune responses, and energy expended to thermoregulate. Many of these effects persisted days to weeks after hatching. In most cases, ducklings that hatched from eggs incubated at lowest temperature performed poorer than ducklings that hatched from eggs incubated at the higher temperatures. Incubation temperature also affected wood duck embryonic developmental trajectories and energy expended during incubation with embryos from the low incubation temperature expended more energy and developing slower than ducklings incubated at the higher temperatures. Embryonic energy expenditure could contribute to effects observed on hatchling phenotype. Because I demonstrate that incubation temperature affects hatchling phenotypic quality, the variability upon which natural selection acts, my findings have implications for avian ecology, life history evolution and conservation. / Ph. D.

Immunity and reproduction are important and costly life-history traits and a large part of eco-immunology focuses on trade-offs between investing in reproduction versus immunity. Male Cape ground squirrels (Xerus inauris) are a good organism to test these trade-offs as they invest heavily in sperm competition, evidenced by their large testes, and exhibit alternative reproductive tactics. My research objective was to determine 1) if testosterone suppresses immunity, or if immunity suppresses testosterone, and 2) if alternative reproductive tactics differ in their investments in immunity and reproduction. I found evidence that testosterone was suppressed after an immune challenge, and that manipulatively increased testosterone had no effect on immunity, body condition or parasites. The dispersing tactic males were in worse condition, had higher parasite abundances, but showed no difference in their innate immune ability to non-dispersing males. Males incur increased costs with dispersal and may focus their energy into reproduction instead of immunity. / October 2015

Le cancer est un problème majeur en santé humaine représentant l’une des principales causes de décès dans le monde. Depuis le début du 20ème siècle, le parasitisme a émergé comme un facteur déterminant pour expliquer la vulnérabilité face au cancer, avec un nombre croissant d’agents infectieux reconnus comme oncogènes. En parallèle, les virus oncolytiques ont attiré une attention considérable pour leur intérêt thérapeutique. Cependant, le rôle des autres agents infectieux dans le développement du cancer est resté largement inexploré même s’ils sont l’un comme l’autre soumis aux pressions du système immunitaire. Ainsi, l’objectif de cette thèse a été d’évaluer l’implication des communautés d’agents infectieux, non-oncogènes et non-oncolytiques, dans le processus cancéreux. Grâce à un modèle de tumeur chez la drosophile, nous avons pu démontrer que les infections sont capables de modifier l’équilibre du système immunitaire avec des conséquences significatives sur l’accumulation des cellules cancéreuses. Considérant que les humains sont exposés à de nombreuses infections de manière successive ou concomitante au cours de leur vie, nous avons pu montrer que l’histoire personnelle d’infection module le risque cancéreux via les perturbations continues qu’elle inflige au système immunitaire. Enfin, les résultats obtenus par l’analyse de jeux de données à l’échelle mondiale suggèrent que les agents infectieux sont également capables d’altérer l’incidence des cancers d’origine infectieuse en interagissant avec les agents oncogènes au sein des communautés infectieuses. À la lumière des interactions réciproques entre infections et cancer, il semble indispensable d’évaluer la pertinence des nouvelles approches de lutte contre le cancer dans le contexte des maladies transmissibles. / Cancer represents a huge public health issue as a major cause of death worldwide. Since the beginning of the 20th century, parasitism has emerged as a fundamental mechanism for cancer causation with a growing number of infectious agents recognized as oncogenic. Meanwhile, oncolytic viruses have also attracted considerable interest as possible agents of tumor control. Nevertheless, the role of other infectious agents in cancer development has been largely neglected even if they are both exposed to immune system pressures. Thus, the main objective of this PhD was to evaluate the implication of infectious communities, formed by non-oncogenic and non-oncolytic agents, in carcinogenesis. Using a drosophila tumor model, we demonstrated that infections are able to jeopardize immune system responses in a way that significantly impacts cancer cell accumulation. Considering that humans are exposed to a myriad of infectious agents both successively and concomitantly throughout their lives, we have shown that personal history of infection can alter cancer risk through continuous perturbations of the immune system. Finally, results obtained from the analysis of worldwide databases have suggested that infections are able to mold population-level incidences of cancers with an infectious origin, through their interactions with oncogenic agents in infectious communities. In light of the reciprocal interactions between cancer and infections, new anit-cancer therapeutic strategies should be evaluated in the context of co-occurring transmissible diseases.

Face 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 vieillissement / 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 aging

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