Morger Jennifer, Bajnok Jaroslav, Boyce Kellyanne, Craig Philip S, Rogan Michael T, Lun Zhao-Rong, Hide Geoff, Tschirren Barbara
Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Ecosystems and Environment Research Centre and Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Salford M5 4WT, UK.
Infect Genet Evol. 2014 Aug;26:180-4. doi: 10.1016/j.meegid.2014.05.032. Epub 2014 Jun 6.
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.
刚地弓形虫是一种极为成功的寄生虫，在全球范围内广泛流行。小型啮齿动物是其主要中间宿主，且越来越多的证据表明刚地弓形虫会改变它们的行为。慢性感染的啮齿动物学习能力受损、活动增强，最重要的是，对猫气味的先天恐惧降低。宿主行为的这种改变确保了刚地弓形虫从啮齿动物成功传播至猫科动物，即该寄生虫的终末宿主。鉴于这种行为操纵对健康的负面影响，以及感染急性期死亡率的增加，我们预计啮齿动物会进化出有效的抵抗机制来预防或控制感染。事实上，对实验室小鼠的研究已经确定了刚地弓形虫抗性的候选基因。特别重要的似乎是先天免疫受体Toll样受体11（TLR11）和Toll样受体12（TLR12），它们识别刚地弓形虫肌动蛋白结合蛋白并启动针对该寄生虫的免疫反应。在此，我们分析了野生林鼠（Apodemus sylvaticus）自然种群中TLR11和TLR12的遗传多样性，并测试TLR11和TLR12多态性与刚地弓形虫感染之间的关联，以及TLR11和TLR12在感染状态上的上位相互作用。我们发现TLR11和TLR12在林鼠中均具有多态性，分别有四种和九种氨基酸单倍型。然而，我们没有发现证据表明TLR11或TLR12的基因型或单倍型与弓形虫感染显著相关。尽管TLR11和TLR12在刚地弓形虫识别和免疫防御启动中很重要，但TLR11和TLR12的自然多态性在介导野生林鼠自然宿主种群对刚地弓形虫的定性抗性中似乎只起次要作用。这突出了在具有生态意义的背景下评估在实验室环境中鉴定的寄生虫抗性候选基因的作用的重要性，以量化它们在介导野生宿主 - 寄生虫相互作用中的作用。
