Feeding Immunity: Physiological and Behavioral Responses to Infection and Resource Limitation

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.

Parasite resource manipulation drives bimodal variation in infection duration

“…the fatassociated hormone leptin) and induced immunity (e.g. the cytokine interleukin (IL)-13, a promotor of helminth clearance) in our rewilded mouse experiment (electronic supplementary material, figure S1) [24,33], as well as by previous laboratory experiments (reviewed in [34]) and wildlife experiments [35]. The rate of resource flow to induced immunity is a function of response-fuelling reversible mass and response-provoking parasite biomass, defined as bRP, with b as the biomass flow rate per gram parasite [10].…”

Rapid environmental effects on gut nematode susceptibility in rewilded mice

“…Controlled laboratory studies (e.g., [ 15 , 17 , 18 ]) suggest that microbial exposure is the crucial aspect of nature that is missing from most of laboratory immunology, but the impact of microbes in an otherwise natural context remains unknown. Our experimental approach of putting mice on “farms” exposes them to environmental microbial diversity but also to other natural challenges, including the need to navigate a complex environment, find and build shelter, and endure variable weather conditions [ 24 ]. Importantly, we controlled for temperature and humidity differences between the laboratory and field so that we could rule out simple thermal preferences (which, for mice, is around 30°C [ 25 ], well above the usual “mouse house” temperature of 20–22°C) as a cause of any difference between susceptibility phenotypes in the laboratory versus field.…”

Physiological dynamics, reproduction‐maintenance allocations, and life history evolution

“…Investment in cellular defense reflects prioritization of self-maintenance over reproduction when the trade-off is exacerbated by limits on resource acquisition. More recently, work on (rewilded) mice and the interaction between foraging, resource levels, and parasite burdens revealed a complex nexus of interactions mediated by resources, immunity, and ecology (Budischak et al, 2018).…”

“…More recently, work on (rewilded) mice and the interaction between foraging, resource levels, and parasite burdens revealed a complex nexus of interactions mediated by resources, immunity, and ecology (Budischak et al, 2018). More recently, work on (rewilded) mice and the interaction between foraging, resource levels, and parasite burdens revealed a complex nexus of interactions mediated by resources, immunity, and ecology (Budischak et al, 2018).…”