Parasites are arguably among the strongest drivers of natural selection, constraining hosts to evolve resistance and tolerance mechanisms. Although, the genetic basis of adaptation to parasite infection has been widely studied, little is known about how epigenetic changes contribute to parasite resistance and eventually, adaptation. Here, we investigated the role of host DNA methylation modifications to respond to parasite infections. In a controlled infection experiment, we used the three-spined stickleback fish, a model species for host–parasite studies, and their nematode parasite Camallanus lacustris. We showed that the levels of DNA methylation are higher in infected fish. Results furthermore suggest correlations between DNA methylation and shifts in key fitness and immune traits between infected and control fish, including respiratory burst and functional trans-generational traits such as the concentration of motile sperm. We revealed that genes associated with metabolic, developmental, and regulatory processes (cell death and apoptosis) were differentially methylated between infected and control fish. Interestingly, genes such as the neuropeptide FF receptor 2 and the integrin alpha 1 as well as molecular pathways including the Th1 and Th2 cell differentiation were hypermethylated in infected fish, suggesting parasite-mediated repression mechanisms of immune responses. Altogether, we demonstrate that parasite infection contributes to genome-wide DNA methylation modifications. Our study brings novel insights into the evolution of vertebrate immunity and suggests that epigenetic mechanisms are complementary to genetic responses against parasite-mediated selection.

中文翻译：

---

实验性寄生虫感染导致全基因组 DNA 甲基化变化。

寄生虫可以说是自然选择最强大的驱动力之一，限制宿主进化出抵抗和耐受机制。尽管适应寄生虫感染的遗传基础已被广泛研究，但对于表观遗传变化如何促进寄生虫抵抗力并最终促进适应却知之甚少。在这里，我们研究了宿主 DNA 甲基化修饰在应对寄生虫感染方面的作用。在一项受控感染实验中，我们使用了宿主寄生虫研究的模型物种三刺刺鱼及其线虫寄生虫Camallanus lacustris。我们发现受感染的鱼的 DNA 甲基化水平较高。研究结果还表明，DNA 甲基化与受感染鱼和对照鱼之间关键健康和免疫特征的变化之间存在相关性，包括呼吸爆发和功能性跨代特征，例如活动精子的浓度。我们发现，与代谢、发育和调节过程（细胞死亡和细胞凋亡）相关的基因在感染鱼和对照鱼之间存在差异甲基化。有趣的是，神经肽 FF 受体 2和整合素 α 1等基因以及包括 Th1 和 Th2 细胞分化在内的分子途径在受感染的鱼中高度甲基化，表明寄生虫介导的免疫反应抑制机制。总而言之，我们证明寄生虫感染有助于全基因组 DNA 甲基化修饰。我们的研究为脊椎动物免疫的进化带来了新的见解，并表明表观遗传机制与针对寄生虫介导的选择的遗传反应是互补的。