Genetic variation in host resistance and susceptibility to pathogens plays a key role in the ecology and evolution of infectious diseases. Screening animal populations for associations between immunity genes and pathogens allows scientists to identify the candidate genes that underlie variation in disease resistance and pathology. The Toll-like receptors are a family of innate immune receptors that recognize different classes of highly conserved pathogen molecules. Examples include bacterial cell wall components (lipopolysaccharides, peptidoglycan), bacterial flagellin, and double-stranded RNA. Toll-like receptor 2 (TLR2) is important for recognizing bacterial lipoproteins. The Lyme disease pathogen, Borrelia burgdorferi sensu lato, expresses dozens of lipoproteins inside the vertebrate host and the TLR2 receptor is therefore critical for recognizing and controlling the intensity of infections. The bank vole, Myodes glareolus, is an important host for the European Lyme disease pathogen B. afzelii. Populations of bank voles are polymorphic for the TLR2 receptor [1] and a field study in Sweden found an association between the TLR2 genotype and the probability of infection with B. afzelii [2]. A recent study found a strong correlation between the frequency of the TLR2 resistance allele in European bank vole populations and the incidence of human Lyme disease [3]. This study suggested that the B. afzelii pathogen is driving the evolution of the TLR2 polymorphism in the bank vole [3].
The purpose of my Master thesis was to test whether the bank vole population in Neuchatel was polymorphic at the TLR2 locus and whether this polymorphism was associated with the probability of infection with B. afzelii. In the fall of 2014, I captured 36 wild bank voles in the forest above Neuchâtel. Genotyping of the TLR locus found that the Neuchâtel bank vole population contained the susceptible C1 cluster and the C3 cluster (rare in Sweden), but not the resistant C2 cluster. Of the 36 bank voles, only three were infected with B. afzelii and these belonged to all three possible TLR2 genotypes: C1/C1, C1/C3, and C3/C3. Thus my Master thesis confirmed that the Neuchatel bank vole population is polymorphic at the TLR2 gene but was inconclusive with respect to whether the TLR2 locus mediates susceptibility or resistance to the Lyme disease pathogen B. afzelii. I am currently helping Andrea Gomez, a PhD student in the lab, to conduct experimental infection studies on laboratory-born bank voles. We are challenging pathogen-free, lab-born bank voles to infectious challenge with Ixodes ricinus nymphs that were experimentally infected with a strain of B. afzelii that is very common in the local area. The goal of this research is to test whether there is a causal link between the TLR2 polymorphism and the probability of becoming infected following exposure to B. afzelii-infected ticks.

References:

1. Tschirren B, Andersson M, Scherman K, Westerdahl H, Raberg L, Råberg L: Contrasting patterns of diversity and population differentiation at the innate immunity gene toll-like receptor 2 (TLR2) in two sympatric rodent species. Evolution 2012, 66(3):720-731.
2. Tschirren B, Andersson M, Scherman K, Westerdahl H, Mittl PRE, Raberg L: Polymorphisms at the innate immune receptor TLR2 are associated with Borrelia infection in a wild rodent population. Proceedings of the Royal Society B-Biological Sciences 2013, 280(1759):20130364.
3. Tschirren B: Borrelia burgdorferi sensu lato infection pressure shapes innate immune gene evolution in natural rodent populations across Europe. Biology Letters 2015, 11(5).