Pathogen-associated selection on innate immunity genes (TLR4, TLR7) in a neotropical rodent in landscapes differing in anthropogenic disturbance

Alexander Christoph Heni,Simone Sommer,Christian Drosten,Andrea Rasche,Victor Max Corman,Julian Schmid

doi:10.1038/s41437-020-0331-y

Abstract

Toll-like receptors (TLRs) form part of the innate immune system and can recognize structurally conserved pathogen-associated molecular pattern (PAMP) molecules. Their functional importance in the resistance to pathogens has been documented in laboratory experimental settings and in humans. TLR diversity, however, has been rarely investigated in wildlife species. How the genetic diversity of TLRs is associated with various pathogens and how it is shaped by habitat disturbance are understudied. Therefore, we investigated the role of genetic diversity in the functionally important parts of TLR4 and TLR7 genes in resistance towards gastrointestinal nematodes and Hepacivirus infection. We chose a generalist study species, the rodent Proechimys semispinosus, because it is highly abundant in three Panamanian landscapes that differ in their degree of anthropogenic modification. We detected only two TLR7 haplotypes that differed by one synonymous single-nucleotide polymorphism (SNP) position. The TLR4 variability was higher, and we detected four TLR4 haplotypes that differed at one synonymous SNP and at three amino acid positions within the leucine-rich repeat region. Only TLR4 haplotypes had different frequencies in each landscape. Using generalized linear models, we found evidence that nematode loads and virus prevalence were influenced by both specific TLR4 haplotypes and landscape. Here, the variable “landscape” served as a surrogate for the important influential ecological factors distinguishing landscapes in our study, i.e. species diversity and host population density. Individuals carrying the common TLR4_Ht1 haplotype were less intensely infected by the most abundant strongyle nematode. Individuals carrying the rare TLR4_Ht3 haplotype were all Hepacivirus-positive, where those carrying the rare haplotype TLR4_Ht4 were less often infected by Hepacivirus than individuals with other haplotypes. Our study highlights the role of TLR diversity in pathogen resistance and the importance of considering immune genetic as well as ecological factors in order to understand the effects of anthropogenic changes on wildlife health.

Highlights

Deforestation, agricultural encroachment, and urbanization often result in the alteration of pathogen communities and contact probability between wildlife, livestock, and humans, thereby affecting transmission and host infection patterns in multiple ways that are often intimately intertwined (Jones et al 2008)
Since high major histocompatibility complex (MHC) polymorphism is maintained by pathogen-driven selection either because of the effects of specific MHC alleles (“rare allele advantage hypothesis” or “frequency-dependent selection”, Clarke and Kirby 1966) because of an advantage of heterozygote individuals (“heterozygote advantage”, Doherty and Zinkernagel 1975), we have tested whether the “rare allele advantage hypothesis/frequency-dependent selection” or “heterozygote advantage” better explains the variance in gastrointestinal nematode loads and Hepacivirus resistance. Since both pathogen loads and host genetic diversity are affected by habitat alterations and associated ecological and environmental modifications, we investigated whether associations between Toll-like receptors (TLRs) diversity and pathogen load remain stable or might be even stronger once additional landscape-specific ecological attributes are taken into account
Studies on TLRs' molecular evolutionary dynamics have revealed, that selective pressures vary between the TLRs and taxa, and, to date, the role of TLR polymorphism and the type of selection that shapes this polymorphism in natural host populations is poorly understood (Grueber et al 2012; Tschirren et al 2013; Babik et al 2014), when compared with their adaptive counterparts, namely the MHC receptors, of the adaptive branch of the immune system

Summary

Introduction

Deforestation, agricultural encroachment, and urbanization often result in the alteration of pathogen communities and contact probability between wildlife, livestock, and humans, thereby affecting transmission and host infection patterns in multiple ways that are often intimately intertwined (Jones et al 2008). Environmental change leading to a reduced habitat size and increasing habitat isolation can impact ecologically important host community and population traits such as species diversity and host population densities, facilitating the transmission of pathogens (Schmid et al 2018). Habitat disturbance can affect the individual host immune genetic constitution by increasing population isolation, and inhibit gene flow between subpopulations (Sommer 2005). Our knowledge about the functional importance of adaptive genetic diversity in wildlife health when both pathogen loads and host genetic diversity are affected by habitat alterations and associated ecological and environmental modifications is limited. Populations with a large MHC allele repertoire display lower parasite loads (Meyer-Lucht and Sommer 2009)

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