The Kielder Forest field vole project

Individuals vary in their response to infectious disease. Beyond recognizing that such variation exists in natural populations, though, we understand little of the genetic and physiological basis of this variation, and the health and fitness consequences. Improving this understanding is a key step towards predicting which individuals are, for example, most vulnerable to infectious disease. 

To address this, from 2015-2020, I studied a natural population of field voles, Microtus agrestis, as part of a large Natural Environment Research Council (NERC) grant. This project resulted in a large and complex dataset for over 3,000 individually-marked wild rodents from multiple sites. This dataset included both longitudinal and cross-sectional components and included multiple parasite measures (micro and macroparasites), multiple measures of the immune response (RNASeq data and more targeted qPCR data) as well as immunogenetic data (genotyping data for over 300 SNPs).

HOW TO INDIVIDUALS VARY IMMUNOLOGICALLY?

We identified, for the firts time, consistent individual differences in immunity, or what you might call ‘immune personalities’, in the wild. See the press-release for this work. 

We also identified genes which display particularly high individual variability in their transcriptional response to immune challenge, and could be used as markers of immune response in larger studies. 

WHY DO INDIVIDUALS VARY IMMUNOLOGICALY?

We identified a candidate gene for a tolerant immune response. Tolerance, like resistance, is an active response to infection that minimises the disease pathology caused by infection (rather than preventing or clearing an infection). This work has potential implications for disease control as it may facilitate the identification of high-risk tolerant individuals who can act as superspreaders, allowing more targeted control. 

Our work also provided evidence for experiences early in life (e.g. early infections) shaping individual immune phenotypes.

WHAT ARE THE CONSEQUENCES OF THIS IMMUNOLOGICAL VARIATION?

We showed that the expression of certain immune genes in early life is associated with later life measures of success in the wild. More specifically, we showed that early life expression of Interleukin-17 (Il17) was associated with reproductive success later in life. We also showed that early life expression of Interleukin-10 (Il10) was associated with later life infection with a chronic bacterial infection. 

Our work showed evidence for divergent, sex-specific outcomes of the same immune gene polymorphism. We observed these divergent outcomes at multiple levels - from immunity to health and ultimately, fitness.