Effects of an IgE receptor polymorphism acting on immunity, susceptibility to infection and reproduction in a wild rodent
Effects of an IgE receptor polymorphism acting on immunity, susceptibility to infection and reproduction in a wild rodent
复制标题
IgE 受体多态性对野生啮齿动物免疫、感染易感性和繁殖的影响
DOI：
10.1101/841825
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Wanelik K
中科院分区：
文献类型：
--
作者：
Wanelik K
个体的基因型是其免疫功能的重要预测因子，随后，他们控制或避免感染的能力，并最终将后代传给下一代。然而，相同的基因型，受到不同的环境，也可能导致不同的结果。两性代表着两种不同的环境。两性二态现象在动物界普遍存在。尽管如此，在健康和疾病的背景下，性别对基因型表达的重要性知之甚少，特别是在自然种群中。我们在田鼠（Microtus agrestis）自然种群中发现了高亲和力免疫球蛋白E （IgE）受体（GC和非GC单倍型）的同义性多态性，该多态性对个体的免疫基因表达、感染易感性和繁殖成功率具有性别特异性影响。我们发现GC单倍型对影响炎症的基因表达的影响与性别有显著的相互作用。具有GC单倍型的雄性具有上调的促炎基因，特别是促炎细胞因子il33，而雌性具有上调的抗炎基因，特别是抗炎细胞因子抑制剂soc3。此外，我们发现GC单倍型对一种常见的微寄生虫巴贝虫感染概率的影响与性别有显著的相互作用。具有GC单倍型的雄性对感染的易感性差异不显著，而具有GC单倍型的雌性更容易被感染。最后，我们发现GC单倍型对繁殖成功的影响也表现出与性别的显著交互作用。具有GC单倍型的雄性具有较低的繁殖成功率，而具有GC单倍型的雌性在其产生的后代数量上没有差异。据我们所知，这是首次在自然种群中记录到在所有三个水平（免疫基因表达、对感染的易感性和繁殖成功）上具有性别特异性影响的多态性。
The genotype of an individual is an important predictor of their immune function, and subsequently, their ability to control or avoid infection and ultimately contribute offspring to the next generation. However, the same genotype, subjected to different environments, can also result in different outcomes. The sexes represent two such different environments. Sexual dimorphism is widespread across the animal kingdom. Despite this, very little is known about the importance of sex for the expression of genotype in the context of health and disease, particularly in natural populations. We identified a synonymous polymorphism in the high-affinity Immunoglobulin E (IgE) receptor (GC and non-GC haplotypes) that has sex-specific effects on immune gene expression, susceptibility to infection and reproductive success of individuals in a natural population of field voles (Microtus agrestis). We found that the effect of the GC haplotype on the expression of genes affecting inflammation displayed a significant interaction with sex. While males with the GC haplotype had upregulated pro-inflammatory genes, in particular the pro-inflammatory cytokineIl33, females had upregulated anti-inflammatory genes, in particular the anti-inflammatory cytokine inhibitorSocs3. Furthermore we found that the effect of the GC haplotype on the probability of infection with a common microparasite,Babesia microti, displayed a significant interaction with sex. While males with the GC haplotype did not differ significantly in their susceptibility to infection, females with the GC haplotype were more likely to be infected. Finally, we found that the effect of the GC haplotype on reproductive success also displayed a significant interaction with sex. While males with the GC haplotype had a lower reproductive success, females with the GC haplotype did not differ in the number of offspring they produced. To our knowledge, this is the first time that a polymorphism with sex-specific effects across all three levels (immune gene expression, susceptibility to infection and reproductive success) has been documented in a natural population.