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

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.

Disentangling direct from indirect effects of habitat disturbance on multiple components of biodiversity

“…This method identified 14 different egg morphotypes (i.e. at least 14 different intestinal helminth species) in faeces of P. semispinosus (details in Heni et al, 2020). We calculated the exponential of Shannon parasite entropy (Hill numbers with q = 1) for each P. semispinosus individual by using the package ‘ diverse ’ v.0.1.5 (Guevara et al, 2016).…”

Pathogen‐mediated selection favours the maintenance of innate immunity gene polymorphism in a widespread wild ungulate

“…This supports the general idea that different habitats in terms of biotic and abiotic factors are likely to support distinct pathogen communities and so distinct pathogen‐mediated‐selection regime as observed for Mhc (Alcaide et al., 2008; Eizaguirre & Lenz, 2010; Hedrick, 2002). Further data using longer time series are required to explicitly test whether Toxoplasma and Chlamydia prevalence are negatively correlated in space and/or time, which is a prerequisite for investigating whether selection pressures are fluctuating (Spurgin & Richardson, 2010; Heni et al, 2020).…”

“…A multitude of studies have revealed associations between Tlr gene polymorphism and infectious diseases in humans and domestic species (Mun et al., 2003; Yang & Joyee, 2008). However, very few (most focussing on birds or rodents) have investigated their role in host‐pathogen interactions in natural environments and their contemporary mechanisms of evolution at a population level (but Heni et al, 2020; Kloch et al., 2018).…”

“…Most immunity‐related genes have pleiotropic effects on resistance against several pathogens (Hedrick, 1999) and the maintenance of “susceptible” (deleterious) alleles in a wild population can be due to antagonist effects of a given immunity‐related gene on several pathogens (i.e., antagonistic pleiotropy). To date, the great majority of studies examining the selective effects of multiple pathogens on host immunogenetic patterns focussed on Mhc genes (Tollenaere et al., 2008 on voles; Loiseau et al., 2008 on house sparrows; Kamath et al., 2014 in plain zebras; Froeschke & Sommer, 2012 on striped mouse but see Antonides et al., 2019 in bananaquit and Heni et al, 2020 in neotropical rodents).…”

Roles of TLR7 in Schistosoma japonicum Infection-Induced Hepatic Pathological Changes in C57BL/6 Mice

“…TLR7 is an endosomal TLR that recognizes single-stranded RNA (ssRNA) and responds to imidazoquinoline compounds such as imiquimod or resiquimod (Ernst et al, 2020). TLR7 was originally identified as a sensor for single stranded RNA (ssRNA) and plays an important role in fighting against pathogens, such as viruses and bacteria (Parra et al, 2018;Heni et al, 2020). In parasite research, TLR7 ccould mediate early innate immune responses to malaria (Baccarella et al, 2013).…”