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.

中文翻译：

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在人为干扰不同的景观中，新热带啮齿动物先天免疫基因（TLR4，TLR7）的病原体相关选择

Toll 样受体 (TLR) 是先天免疫系统的一部分，可以识别结构上保守的病原体相关分子模式 (PAMP) 分子。它们在抵抗病原体方面的功能重要性已在实验室实验环境和人类中得到证实。然而，在野生动物物种中很少研究 TLR 多样性。TLR 的遗传多样性如何与各种病原体相关联，以及它如何受到栖息地干扰的影响，目前尚未得到充分研究。因此，我们研究了遗传多样性在 TLR4 和 TLR7 基因的功能重要部分中对胃肠道线虫和肝炎病毒感染的抵抗力中的作用。我们选择了一个通才研究物种，啮齿动物 Proechimys semispinosus，因为它在巴拿马的三个景观中非常丰富，这些景观的人为改造程度不同。我们仅检测到两种 TLR7 单倍型，它们的同义单核苷酸多态性 (SNP) 位置不同。TLR4 变异性更高，我们检测到四种 TLR4 单倍型，它们在一个同义 SNP 和富含亮氨酸的重复区域内的三个氨基酸位置处不同。只有 TLR4 单倍型在每个景观中具有不同的频率。使用广义线性模型，我们发现有证据表明线虫负荷和病毒流行率受到特定 TLR4 单倍型和景观的影响。在这里，变量“景观”作为我们研究中区分景观的重要影响生态因素的替代品，即物种多样性和宿主种群密度。携带常见 TLR4_Ht1 单倍型的个体被最丰富的圆线虫感染的强度较低。携带稀有 TLR4_Ht3 单倍型的个体都是肝炎病毒阳性的，其中携带稀有单倍型 TLR4_Ht4 的个体比具有其他单倍型的个体更少感染肝炎病毒。我们的研究强调了 TLR 多样性在病原体抗性中的作用以及考虑免疫遗传和生态因素的重要性，以了解人为变化对野生动物健康的影响。携带稀有单倍型 TLR4_Ht4 的人感染肝炎病毒的频率低于携带其他单倍型的个体。我们的研究强调了 TLR 多样性在病原体抗性中的作用以及考虑免疫遗传和生态因素的重要性，以了解人为变化对野生动物健康的影响。携带稀有单倍型 TLR4_Ht4 的人感染肝炎病毒的频率低于携带其他单倍型的个体。我们的研究强调了 TLR 多样性在病原体抗性中的作用以及考虑免疫遗传和生态因素的重要性，以了解人为变化对野生动物健康的影响。