title: Naturally occurring Toll-like receptor 11 (TLR11) and Toll-like receptor 12 (TLR12) polymorphisms are not associated with Toxoplasma gondii infection in wild wood mice.
abstract: Toxoplasma gondii is a highly successful parasite with a worldwide prevalence. Small rodents are the main intermediate hosts, and there is growing evidence that T. gondii modifies their behaviour. Chronically infected rodents show impaired learning capacity, enhanced activity, and, most importantly, a reduction of the innate fear towards cat odour. This modification of host behaviour ensures a successful transmission of T. gondii from rodents to felids, the definitive hosts of the parasite. Given the negative fitness consequences of this behavioural manipulation, as well as an increased mortality during the acute phase of infection, we expect rodents to evolve potent resistance mechanisms that prevent or control infection. Indeed, studies in laboratory mice have identified candidate genes for T. gondii resistance. Of particular importance appear to be the innate immune receptors Toll-like receptor 11 (TLR11) and Toll-like receptor 12 (TLR12), which recognise T. gondii profilin and initiate immune responses against the parasite. Here we analyse the genetic diversity of TLR11 and TLR12 in a natural population of wood mice (Apodemus sylvaticus), and test for associations between TLR11 and TLR12 polymorphisms and T. gondii infection, as well as for epistatic interactions between TLR11 and TLR12 on infection status. We found that both TLR11 and TLR12 were polymorphic in wood mice, with four and nine amino acid haplotypes, respectively. However, we found no evidence that TLR11 or TLR12 genotypes or haplotypes were significantly associated with Toxoplasma infection. Despite the importance of TLR11 and TLR12 in T. gondii recognition and immune defence initiation, naturally occurring polymorphisms at TLR11 and TLR12 thus appear to play a minor role in mediating qualitative resistance to T. gondii in natural host populations of A. sylvaticus. This highlights the importance of assessing the role of candidate genes for parasite resistance identified in a laboratory setting in an ecologically meaningful context to quantify their role in mediating host-parasite interactions in the wild.
authors.affiliation: Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Morger
authors.affiliation: Ecosystems and Environment Research Centre and Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Salford M5 4WT, UK.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Bajnok
authors.affiliation: Ecosystems and Environment Research Centre and Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Salford M5 4WT, UK.
authors.forename: Kellyanne
authors.initials: K
authors.lastname: Boyce
authors.affiliation: Ecosystems and Environment Research Centre and Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Salford M5 4WT, UK.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Craig
authors.affiliation: Ecosystems and Environment Research Centre and Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Salford M5 4WT, UK.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Rogan
authors.affiliation: Ecosystems and Environment Research Centre and Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Salford M5 4WT, UK; Center for Parasitic Organisms, State Key Laboratory of Biocontrol, School of Life Sciences and Key Laboratory of Tropical Disease Control of the Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Zhao-Rong
authors.initials: ZR
authors.lastname: Lun
authors.affiliation: Ecosystems and Environment Research Centre and Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Salford M5 4WT, UK.
authors.forename: Geoff
authors.initials: G
authors.lastname: Hide
authors.affiliation: Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Electronic address: barbara.tschirren@ieu.uzh.ch.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tschirren
mesh_terms: D000818:Animals; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D008969:Molecular Sequence Data; D051189:Murinae; D011110:Polymorphism, Genetic; D012376:Rodent Diseases / Q000235:genetics* / Q000469:parasitology; D051193:Toll-Like Receptors / Q000235:genetics*; D014122:Toxoplasma / Q000302:isolation & purification; D014124:Toxoplasmosis, Animal / Q000235:genetics* / Q000469:parasitology
chemical_list: D051193:Toll-Like Receptors
keywords: Apodemus sylvaticus; Immunogenetics; Parasite resistance; Toll-like receptors; Toxoplasma gondii; Zoonotic disease