Susceptibility to infection with Borrelia afzelii and TLR2 polymorphism in a wild reservoir host

Andrea Gomez-Chamorro,Claire Cayol,Dolores Genné,Tapio Mappes,Esa Koskela,Maarten Jeroen Voordouw,Anouk Sarr,Florian Battilotti,Nathalie Boulanger

doi:10.1038/s41598-019-43160-3

Abstract

The study of polymorphic immune genes in host populations is critical for understanding genetic variation in susceptibility to pathogens. Controlled infection experiments are necessary to separate variation in the probability of exposure from genetic variation in susceptibility to infection, but such experiments are rare for wild vertebrate reservoir hosts and their zoonotic pathogens. The bank vole (Myodes glareolus) is an important reservoir host of Borrelia afzelii, a tick-borne spirochete that causes Lyme disease. Bank vole populations are polymorphic for Toll-like receptor 2 (TLR2), an innate immune receptor that recognizes bacterial lipoproteins. To test whether the TLR2 polymorphism influences variation in the susceptibility to infection with B. afzelii, we challenged pathogen-free, lab-born individuals of known TLR2 genotype with B. afzelii-infected ticks. We measured the spirochete load in tissues of the bank voles. The susceptibility to infection with B. afzelii following an infected tick bite was very high (95%) and did not differ between TLR2 genotypes. The TLR2 polymorphism also had no effect on the spirochete abundance in the tissues of the bank voles. Under the laboratory conditions of our study, we did not find that the TLR2 polymorphism in bank voles influenced variation in the susceptibility to B. afzelii infection.

Highlights

The toll-like receptor 2 (TLR2) recognizes a wide variety of PAMPs including peptidoglycan, zymosan, and lipoproteins[3]
The TLR2 gene sequences of the animals in the experimental infection formed three clearly separated clusters that coded for three different protein variants: cluster 1 (C1), cluster 2 (C2) and cluster 3 (C3); these three clusters were the same as the ones described by Tschirren et al.[13]
The C1 and C2 clusters, C1 and C3 clusters, and C2 and C3 clusters were separated by a genetic distance of 12, 15, and 15 nucleotide differences, respectively, which corresponded to a protein distance of 7, 7, and 4 amino acids, respectively (Fig. S1)

Summary

Introduction

The toll-like receptor 2 (TLR2) recognizes a wide variety of PAMPs including peptidoglycan, zymosan, and lipoproteins[3]. The two aims of this study were to determine whether the TLR2 polymorphism in wild bank voles influences variation in the probability of infection with B. afzelii (hereafter referred to as host susceptibility) and variation in B. afzelii spirochete abundance in host tissues (hereafter referred to as host spirochete load). To test this hypothesis, we challenged Borrelia-free, lab-born bank voles of known TLR2 genotype with B. afzelii via tick bite. The importance of the C3 allele was assessed for the first time in this study

Objectives

Methods

Results

Conclusion