Budischak, Sarah A. and Clayton E. Cressler. “Fueling Defense: Effects of Resources on the Ecology and Evolution of Tolerance to Parasite Infection.” Frontiers in Immunology, 2018, 9:2453.
Abstract: Resource availability is a key environmental constraint affecting the ecology and evolution of species. Resources have strong effects on disease resistance, but they can also affect the other main parasite defense strategy, tolerance. A small but growing number of animal studies are beginning to investigate the effects of resources on tolerance phenotypes. Here, we review how resources affect tolerance strategies across animal taxa ranging from fruit flies to frogs to mice. Surprisingly, resources (quality and quantity) can increase or reduce tolerance, dependent upon the particular host-parasite system. To explore this seeming contradiction, we recast predictions of models of sterility tolerance and mortality tolerance in a resource-dependent context. Doing so reveals that resources can have very different epidemiological and evolutionary effects, depending on what aspects of the tolerance phenotype are affected. Thus, it is critical to consider both sterility and mortality in future empirical studies of how behavioral and environmental resource availability affect tolerance to infection.
Budischak, Sarah A., Christina B. Hansen, Quentin Caudron, Romain Garnier, Tyler R. Kartzinel, István Pelczer, Clayton E. Cressler, Anieke van Leeuwen, and Andrea L. Graham. “Feeding Immunity Physiological and Behavioral Responses to Infection and Resource Limitation.” Frontiers in Immunology, 2018, 8:1914.
Abstract: Resources are a core currency of species interactions and ecology in general (e.g., think of food webs or competition). Within parasite-infected hosts, resources are divided among the competing demands of host immunity and growth as well as parasite reproduction and growth. Effects of resources on immune responses are increasingly understood at the cellular level (e.g., metabolic predictors of effector function), but there has been limited consideration of how these effects scale up to affect individual energetic regimes (e.g., allocation trade-offs), susceptibility to infection, and feeding behavior (e.g., responses to local resource quality and quantity). We experimentally rewilded laboratory mice (strain C57BL/6) in semi-natural enclosures to investigate the effects of dietary protein and gastrointestinal nematode (Trichuris muris) infection on individual-level immunity, activity, and behavior. The scale and realism of this field experiment, as well as the multiple physiological assays developed for laboratory mice, enabled us to detect costs, trade-offs, and potential compensatory mechanisms that mice employ to battle infection under different resource conditions. We found that mice on a low-protein diet spent more time feeding, which led to higher body fat stores (i.e., concentration of a satiety hormone, leptin) and altered metabolite profiles, but which did not fully compensate for the effects of poor nutrition on albumin or immune defenses. Specifically, immune defenses measured as interleukin 13 (IL13) (a primary cytokine coordinating defense against T. muris) and as T. muris-specific IgG1 titers were lower in mice on the low-protein diet. However, these reduced defenses did not result in higher worm counts in mice with poorer diets. The lab mice, living outside for the first time in thousands of generations, also consumed at least 26 wild plant species occurring in the enclosures, and DNA metabarcoding revealed that the consumption of different wild foods may be associated with differences in leptin concentrations. When individual foraging behavior was accounted for, worm infection significantly reduced rates of host weight gain. Housing laboratory mice in outdoor enclosures provided new insights into the resource costs of immune defense to helminth infection and how hosts modify their behavior to compensate for those costs.
Budischak, Sarah A., Dawn O’Neal, Anna E. Jolles, and Vanessa O. Ezenwa. “Differential Host Responses to Parasitism Shape Divergent Fitness Costs of Infection.” Functional Ecology, vol. 32, issue 2, 2018, pp. 324-333.
Abstract: Fitness costs of infection are fundamental to understanding the ecology and evolution of host–parasite interactions. However, these costs, and particularly their underlying mechanisms, are challenging to evaluate in wild populations. Here, we quantified total and species‐specific costs of gastrointestinal worms on African buffalo, by combining the power of an anthelmintic treatment experiment that perturbed the entire worm community with a longitudinal study that tracked the two most dominant community members. Reducing all worms improved buffalo body condition, which was strongly associated with increases in survival and reproduction. Species‐specific analyses revealed that condition‐mediated fitness costs of infection differed between parasite species. Hosts that gained the blood‐sucking worm Haemonchus, lost condition, and this loss may have been mediated by reductions in forage intake. Hosts that resisted Haemonchus by elevating IL‐4 and eosinophil immune defences were able to reduce their parasite loads and gain back condition. Conversely, hosts that gained Cooperia, a less pathogenic worm, gained condition and had higher survival and reproductive success. Elevating immune defences had no effect on Cooperia abundance. Coupled with the positive relationship observed between Cooperia and host condition, our data suggest that hosts might benefit from tolerating Cooperia rather than incurring the costs of resistance. Overall, our study reveals that differential host responses to parasites play a key role in mediating the costs of infection.
Budischak, Sarah A., Aprilianto E. Wiria, Firdaus Hamid, Linda J. Wammes, Maria M. M. Kaisar, Lisette van Lieshout, Erliyani Sartono, Taniawati Supali, Maria Yazdanbakhsh, and Andrea L. Graham. “Competing for Blood: The Ecology of Parasite Resource Competition in Human Malaria-Helminth Co-Infections.” Ecology Letters, vol. 21, 2018, pp. 536-545.
Abstract: Ecological theory suggests that co‐infecting parasite species can interact within hosts directly, via host immunity and/or via resource competition. In mice, competition for red blood cells (RBCs) between malaria and bloodsucking helminths can regulate malaria population dynamics, but the importance of RBC competition in human hosts was unknown. We analysed infection density (i.e. the concentration of parasites in infected hosts), from a 2‐year deworming study of over 4000 human subjects. After accounting for resource‐use differences among parasites, we find evidence of resource competition, priority effects and a competitive hierarchy within co‐infected individuals. For example reducing competition via deworming increased Plasmodium vivaxdensities 2.8‐fold, and this effect is limited to bloodsucking hookworms. Our ecological, resource‐based perspective sheds new light into decades of conflicting outcomes of malaria–helminth co‐infection studies with significant health and transmission consequences. Beyond blood, investigating within‐human resource competition may bring new insights for improving human health.
Dallas, Tad A., A. Alonso Aguirre, Sarah Budischak, Colin Carlson, Vanessa Ezenwa, Barbara Han, Shan Huang, and Patrick R. Stephens. “Gauging Support for Macroecological Patterns in Helminth Parasites.” Global Ecology and Biogeography, vol. 27, issue 12, 2018, pp. 1437-1447.
Abstract: To explore spatial patterns of helminth parasite diversity, and to investigate three main macroecological patterns – (a) latitude–diversity relationships, (b) positive scaling between parasite and host diversity, and (c) species–area relationships – using a largely underutilized global database of helminth parasite occurrence records. We examined the London Natural History Museum’s collection of helminth parasite occurrence records, consisting of over 18,000 unique host species and 27,000 unique helminth parasite species distributed across over 350 distinct terrestrial and aquatic localities. We find support for latitudinal gradients in parasite diversity and a strong relationship between host and parasite diversity at the global scale. Helminth species diversity–area relationships were not detectable as a function of host body mass, but larger geographic areas supported higher parasite richness, potentially mediated through higher host richness. Our findings indicate that helminth parasites may obey some of the macroecological relationships found in free‐living species, suggesting that parasites may offer further support for the generality of these patterns, while offering interesting counterexamples for others. We conclude with a discussion of future directions and potential challenges in the newly emerging macroecology of infectious disease.
Leung, Jacqueline M., Sarah A. Budischak, Hao Chung The, Christina Hansen, Rowann Bowcutt, Rebecca Neill, Mitchell Shellman, P’ng Loke, and Andrea L. Graham. “Rapid Environmental Effects on Gut Nematode Susceptibility in Rewilded Mice.” PLoS Biology, vol. 16, issue 3, 2018, e2004108.
Abstract: Genetic and environmental factors shape host susceptibility to infection, but how and how rapidly environmental variation might alter the susceptibility of mammalian genotypes remains unknown. Here, we investigate the impacts of seminatural environments upon the nematode susceptibility profiles of inbred C57BL/6 mice. We hypothesized that natural exposure to microbes might directly (e.g., via trophic interactions) or indirectly (e.g., via microbe-induced immune responses) alter the hatching, growth, and survival of nematodes in mice housed outdoors. We found that while C57BL/6 mice are resistant to high doses of nematode (Trichuris muris) eggs under clean laboratory conditions, exposure to outdoor environments significantly increased their susceptibility to infection, as evidenced by increased worm burdens and worm biomass. Indeed, mice kept outdoors harbored as many worms as signal transducer and activator of transcription 6 (STAT6) knockout mice, which are genetically deficient in the type 2 immune response essential for clearing nematodes. Using 16S ribosomal RNA sequencing of fecal samples, we discovered enhanced microbial diversity and specific bacterial taxa predictive of nematode burden in outdoor mice. We also observed decreased type 2 and increased type 1 immune responses in lamina propria and mesenteric lymph node (MLN) cells from infected mice residing outdoors. Importantly, in our experimental design, different groups of mice received nematode eggs either before or after moving outdoors. This contrasting timing of rewilding revealed that enhanced hatching of worms was not sufficient to explain the increased worm burdens; instead, microbial enhancement and type 1 immune facilitation of worm growth and survival, as hypothesized, were also necessary to explain our results. These findings demonstrate that environment can rapidly and significantly shape gut microbial communities and mucosal responses to nematode infections, leading to variation in parasite expulsion rates among genetically similar hosts.