LAUSR

Toll-like receptors (TLRs) are important initiators of innate immune responses that target host-pathogen interactions. However, further research into the molecular characteristics of TLRs in wild populations is required, as well as how TLRs genetically influenced pathogen infections in the brown rat (Rattus norvegicus). Here, we explored the genetic characterization and evolution of two sensing nucleic acid TLRs (TLR7 and TLR8) and two sensing non-nucleic acid TLRs (TLR2 and TLR4) in the wild brown rat, and assessed their associations with two RNA viruses (Seoul hantavirus and rat hepatitis E virus (HEV)) and two bacteria (Leptospira and Bartonella). In these four TLRs, we discovered a total of 16 variants. Furthermore, TLR8 had high genetic diversity among 7 variants, while TLR2 had low genetic diversity with only one variant. According to selective pressure analyses, TLR4, TLR7, and TLR8 genes evolved under purifying selection. Interestingly, significant associations were found between three TLR8 variants and HEV infection, as well as one TLR2 variant and Bartonella infection. Overall, our findings provided a glimpse into the genetic characterization of TLRs in the brown rat, and further demonstrated that TLR2 and TLR8 genetic variations were related to Bartonella and HEV infection, respectively. Especially, TLR8 may be a good candidate immune gene for future research on molecular ecology and functional adaptation in wild populations. This article is protected by copyright. All rights reserved.