Epigenetic mechanisms such as DNA methylation and histone post-translational modifications are fundamental for the phenotypic plasticity of insects during their interaction with the environment. In response to environmental cues, the methylation pattern in DNA is dynamically remodeled to achieve an epigenetic control of gene expression. DNA methylation is the focus of study in insects for its evolutionarily conserved character; however, there is scant knowledge about the epigenetic regulation in vector mosquitoes, especially during their infection by parasites. The aim of the present study was to evaluate the participation of DNA methylation in the immune response of Anopheles albimanus to a Plasmodium infection. For this, we first investigated the presence of a fully functional DNA methylation system in A. albimanus by assessing its potential role in larval development. Subsequently, we evaluated the transcriptional response to Plasmodium berghei of two mosquito phenotypes with different degrees of susceptibility to the parasite, in a scenario where their global DNA methylation had been pharmacologically inhibited. Our study revealed that A. albimanus has a functional DNA methylation system that is essential to larval viability, and that is also responsive to feeding and parasite challenges. The pharmacological erasure of the methylome with azacytidine or decitabine abolished the divergent responses of both mosquito phenotypes, leading to a transcriptionally similar response upon parasite challenge. This response was more specific, and the infection load in both phenotypes was lowered. Our findings suggest that DNA methylation may constitute a key factor in vector competence, and a promising target for preventing malaria transmission.

中文翻译：

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白按蚊 DNA 甲基化调节针对伯氏疟原虫的中肠免疫反应。


DNA甲基化和组蛋白翻译后修饰等表观遗传机制是昆虫与环境相互作用过程中表型可塑性的基础。为了响应环境线索，DNA 中的甲基化模式被动态重塑，以实现基因表达的表观遗传控制。 DNA 甲基化因其进化上保守的特性而成为昆虫研究的焦点。然而，人们对媒介蚊子的表观遗传调控知之甚少，特别是在它们被寄生虫感染期间。本研究的目的是评估 DNA 甲基化在白按蚊对疟原虫感染的免疫反应中的参与。为此，我们首先通过评估其在幼虫发育中的潜在作用，研究了 A. albimanus 中是否存在功能齐全的 DNA 甲基化系统。随后，我们评估了两种对寄生虫具有不同程度易感性的蚊子表型对伯氏疟原虫的转录反应，在它们的整体 DNA 甲基化已被药理学抑制的情况下。我们的研究表明，A. albimanus 具有功能性 DNA 甲基化系统，该系统对于幼虫的生存至关重要，并且还能应对摄食和寄生虫的挑战。用氮胞苷或地西他滨对甲基化组进行药物消除消除了两种蚊子表型的不同反应，导致在寄生虫攻击时产生转录相似的反应。这种反应更加特异性，并且两种表型的感染负荷都降低了。我们的研究结果表明，DNA 甲基化可能构成媒介能力的关键因素，也是预防疟疾传播的有希望的目标。