Temporal Anomalies in Immunological Gene Expression in a Time Series of Wild Mice: Signature of an Epidemic?

Abstract

Although the ecological importance of coinfection is increasingly recognized, analyses of microbial pathogen dynamics in wildlife usually focus on an ad hoc subset of the species present due to technological limitations on detection. Here we demonstrate the use of expression profiles for immunological genes (pattern recognition receptors, cytokines and transcription factors) as a means to identify, without preconception, the likelihood of important acute microbial infections in wildlife. Using a wood mouse population in the UK as a model we identified significant temporal clusters of individuals with extreme expression of immunological mediators across multiple loci, typical of an acute microbial infection. These clusters were circumstantially associated with demographic perturbation in the summertime wood mouse population. Animals in one cluster also had significantly higher individual macroparasite burdens than contemporaries with “normal” expression patterns. If the extreme transcriptional profiles observed are induced by an infectious agent then this implicates macroparasites as a possible player in mediating individual susceptibility or resilience to infection. The form of survey described here, combined with next generation nucleic acids sequencing methods for the broad detection of microbial infectious agents in individuals with anomalous immunological transcriptional profiles, could be a powerful tool for revealing unrecognized, ecologically important infectious agents circulating in wildlife populations.

Landscape features and helminth co-infection shape bank vole immunoheterogeneity, with consequences for Puumala virus epidemiology

“…We used b-actin as the endogenous reference gene, as previously validated by Friberg et al (2011) in wood mice. These authors tested a set of nine candidate housekeeping genes in cell cultures and concluded that b-actin was the most stable.…”

Macroparasites at peripheral sites of infection are major and dynamic modifiers of systemic antimicrobial pattern recognition responses

“…This coincided with a sudden turnover in the mouse year classes present, with over‐wintered (1 + ) animals being completely replaced by newly recruited young‐of‐the year (0 + ) (Friberg et al . ). As previously reported (Friberg et al .…”

“…; Friberg et al . ). Captured animals were returned to the laboratory, weighed (g) and housed in identical individual cages under a lighting regimen equivalent to the natural photoperiod at the time of capture.…”

“…Combined dry eye lens weight (g) was used as an estimator of individual age in analyses and also to unambiguously classify over‐wintered (1 + ) and young‐of‐the year (0 + ) cohorts (Friberg et al . ).…”

“…A small set of individuals with very extreme immune expression phenotypes, previously classified in (Friberg et al . ) (possibly linked to an acute, highly immunogenic microbial infection), were excluded from all analyses.…”