Balancing immunity in the face of variable nutritional resources and natural infection in a wild rodent

Supervisors: Dr Amy Pedersen, Dr Simon Babayan

Project Description:

Parasite infections and resource scarcity are common threats to the wellbeing of wild populations and domestic animals. Chronic helminth infections in particular compete with their hosts for nutritional resources, and are a global cause of productivity loss in livestock, estimated at £1.2 billion. Despite the growing knowledge of the dynamics of parasite infection in livestock and wild populations, our understanding of how the host’s immune system mounts and regulates its responses to infection under variable resource availability is limited. This knowledge gap is surprising, given that immune responses are the host’s main defence mechanism against parasites. So far, a major limitation to studying associations between parasite infection, resource scarcity, and immune responses outside of laboratory settings has been the lack of suitable host-parasite systems. In particular, if we want to tease apart the determinants (ecological and demographic factors) of infection by a natural parasite and the immune response in the wild, we need a system in which we can carry out, at the necessary scale, experimental manipulations of parasite infection and food availability both in wild populations and in laboratory settings, with detailed immunological read-outs and natural (i.e. co-evolved) host-parasite combinations. This is especially important for parasite species that cause long-lived, chronic infections, such as helminths — as these parasites survive within the host by directly modulating the immune response and thus form a long-term parasitic association with the host immune system that competes for host nutrients.

We have established a wild mouse—parasite community system in order to study the consequences of infection for host health and fitness. Wood mice (Apodemus sylvaticus) are a very common small mammal in the UK and support a diverse community of helminths (nematodes and cestodes), protozoa, viruses, and bacteria. We have developed the microscopy, immunological and molecular tools to identify >30 unique species, antigen-specific antibodies, and transcriptomes to provide sequences for immune gene expression. Additionally, we have a wild-derived colony of mice and their naturally-infecting parasites, with which we can pair infection/coinfection experiments and varying experimental diets to the wild studies, allowing us to measure and compare immune responses in controlled settings with those in the wild.

Our recent findings suggest that wild mice vary greatly in their general and parasite-specific immune responses and that food supplementation in the wild mitigates the detrimental effects of resource scarcity on survival and reproduction. However, we have yet to test what demographic and ecological factors determine this variation, and importantly, how individuals balance physiological and immunological needs under limited resources when faced with natural infection. The overall aim of this interdisciplinary studentship is to combine ecological field studies, controlled laboratory studies, and classic immunological techniques with novel tools from machine learning in order to identify causal links between food availability, immune responses to infection, and resistance to parasite infection.

These data will provide mechanistic insight into the role of food supplementation, coupled with anthelminthic treatment, improve the control of infection and maintenance of optimal growth. The impact of this research will stretch from ecological to veterinary health circles, and be of primary interest to applied and translational immunologists.

Babayan, S., Wi, L., Hamilton, G., Kilbride, E., Rynkiewicz, E., Clerc, M, and Pedersen, A.B. 2018. The immune and non-immune pathways that drive chronic gastrointestinal helminth burdens in the wild. Frontiers in Immunology, 9, 56.
Pedersen, A.B. and Grieves, T. 2008. The interaction of parasites and resources cause crashes in a wild mouse population. Journal of Animal Ecology 77, 370-377.  
Coltherd, J.C., Babayan, S.A., Bunger, L., Kyriazakis, I., Allen, J.E., and Houdijk, J.G.M. 2011. Interactive effects of protein nutrition, genetic growth potential and Heligmosomoides bakeri infection pressure on resilience and resistance in mice. Parasitology, 138 (10). pp. 1305-1315.

If you wish to apply for this project, please go to this link.