Centro de Investigaciones Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
Front Immunol. 2020 Jan 14;10:3025. doi: 10.3389/fimmu.2019.03025. eCollection 2019.
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 to a infection. For this, we first investigated the presence of a fully functional DNA methylation system in by assessing its potential role in larval development. Subsequently, we evaluated the transcriptional response to 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 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.
表观遗传机制，如 DNA 甲基化和组蛋白翻译后修饰，是昆虫在与环境相互作用过程中表现型可塑性的基础。为了应对环境线索，DNA 中的甲基化模式被动态重塑，以实现对基因表达的表观遗传控制。DNA 甲基化是昆虫研究的焦点，因为它具有进化上保守的特征；然而，关于载体蚊子的表观遗传调控，特别是在寄生虫感染期间的知识甚少。本研究旨在评估 DNA 甲基化在 对 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，来研究 在 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易感性的蚊子表型在其全局 DNA 甲基化被药物抑制的情况下对 的转录反应。我们的研究表明， 具有功能齐全的 DNA 甲基化系统，这对于幼虫的生存至关重要，并且对进食和寄生虫的挑战也有反应。用氮杂胞苷或地西他滨对甲基组进行药理学擦除，消除了两种蚊子表型的不同反应，导致寄生虫挑战时转录反应相似。这种反应更具特异性，两种表型的感染负荷都降低了。我们的研究结果表明，DNA 甲基化可能是媒介能力的关键因素，也是预防疟疾传播的一个有前途的目标。
