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-宿主相互作用-一种表观遗传范例。

-Host Interactions-An Epigenetic Paradigm.

机构信息

Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Taibah University, Madina, Saudi Arabia.

Rajiv Gandhi Technical University, Bhopal, India.

出版信息

Front Immunol. 2019 Mar 22;10:492. doi: 10.3389/fimmu.2019.00492. eCollection 2019.

Abstract

Leishmaniasis is one of the major neglected tropical diseases, for which no vaccines exist. Chemotherapy is hampered by limited efficacy coupled with development of resistance and other side effects. parasites elude the host defensive mechanisms by modulating their surface proteins as well as dampening the host's immune responses. The parasites use the conventional RNA polymerases peculiarly under different environmental cues or pressures such as the host's milieu or the drugs. The mechanisms that restructure post-translational modifications are poorly understood but altered epigenetic histone modifications are believed to be instrumental in influencing the chromatin remodeling in the parasite. Interestingly, the parasite also modulates gene expression of the hosts, thereby hijacking or dampening the host immune response. Epigenetic factor such as DNA methylation of cytosine residues has been incriminated in silencing of macrophage-specific genes responsible for defense against these parasites. Although there is dearth of information regarding the epigenetic alterations-mediated pathogenesis in these parasites and the host, the unique epigenetic marks may represent targets for potential anti-leishmanial drug candidates. This review circumscribes the epigenetic changes during infection, and the epigenetic modifications they enforce upon the host cells to ensure a safe haven. The non-coding micro RNAs as post-transcriptional regulators and correlates of wound healing and toll-like receptor signaling, as well as prognostic biomarkers of therapeutic failure and healing time are also explored. Finally, we highlight the recent advances on how the epigenetic perturbations may impact leishmaniasis vaccine development as biomarkers of safety and immunogenicity.

摘要

利什曼病是主要的被忽视热带病之一,目前尚无疫苗。化疗受到疗效有限、耐药性和其他副作用的阻碍。寄生虫通过调节表面蛋白以及抑制宿主免疫反应来逃避宿主防御机制。寄生虫利用常规 RNA 聚合酶,根据不同的环境线索或压力(如宿主环境或药物)进行独特的调节。尽管改变表观遗传组蛋白修饰被认为在影响寄生虫染色质重塑中起重要作用,但对于重新构建翻译后修饰的机制仍了解甚少。有趣的是,寄生虫还可以调节宿主的基因表达,从而劫持或抑制宿主的免疫反应。表观遗传因子,如胞嘧啶残基的 DNA 甲基化,已被牵连到沉默负责防御这些寄生虫的巨噬细胞特异性基因中。尽管关于这些寄生虫和宿主中表观遗传改变介导的发病机制的信息很少,但独特的表观遗传标记可能代表潜在的抗利什曼病药物候选物的靶点。这篇综述描述了感染过程中的表观遗传变化,以及它们对宿主细胞施加的表观遗传修饰,以确保安全的避难所。还探讨了非编码 microRNAs 作为转录后调节剂以及伤口愈合和 Toll 样受体信号的相关性,以及治疗失败和愈合时间的预后生物标志物。最后,我们强调了最近的进展,即表观遗传扰动如何可能影响利什曼病疫苗开发作为安全性和免疫原性的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/131a/6438953/eb8d8c6c6b32/fimmu-10-00492-g0001.jpg

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