Comparative miRNA transcriptomics of macaques and mice reveals MYOC is an inhibitor for Cryptococcus neoformans invasion into the brain.
Comparative miRNA transcriptomics of macaques and mice reveals MYOC is an inhibitor for Cryptococcus neoformans invasion into the brain.
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猕猴和小鼠的比较 miRNA 转录组学揭示 MYOC 是新型隐球菌侵入大脑的抑制剂
DOI：
10.1080/22221751.2022.2081619
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发表时间：
2022-12
影响因子：
13.2
通讯作者：
中科院分区：
文献类型：
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隐球菌性脑膜脑炎（CM）作为一种感染，在艾滋病患者中正在发生变化，从主要是未接受抗逆转录病毒治疗（ART）的个体转变为有ART治疗经历的个体，同时也出现在新冠病毒（COVID - 19）患者以及免疫功能正常的宿主中。这种真菌感染主要由机会性人类病原体新型隐球菌引起。脑部或中枢神经系统（CNS）的播散是这种疾病最致命的过程；然而，这一过程的潜在机制尚未阐明。此外，由于临床样本的可获取性低，目前隐球菌病临床相关反应的图示有限。在这项研究中，为了探索新型隐球菌感染期间的临床相关反应，采用了猕猴和小鼠感染模型，并进行了微小RNA - 信使RNA转录组分析且将其结合，结果显示细胞骨架（艾滋病患者的一个主要特征）是两种感染模型中受调控的核心通路。值得注意的是，对临床免疫细胞的检测证实艾滋病患者中巨噬细胞“特洛伊木马”现象增强，而这种现象可被细胞骨架抑制剂阻断。此外，由MYOC编码的肌纤蛋白被发现是巨噬细胞“特洛伊木马”的一种新型增强因子，并且在MYOC转基因小鼠的大脑中真菌负荷增加。综上所述，这项研究的结果揭示了细胞骨架和MYOC在真菌中枢神经系统播散中的重要作用，这不仅有助于理解隐球菌性脑膜脑炎在艾滋病患者中的高发病率，还有助于开发针对新型隐球菌及其他病原微生物引起的脑膜脑炎的新型治疗方法。
Cryptococcal meningoencephalitis (CM) is emerging as an infection in HIV/AIDS patients shifted from primarily ARTnaive to ART-experienced individuals, as well as patients with COVID-19 and immunocompetent hosts. This fungal infection is mainly caused by the opportunistic human pathogen Cryptococcus neoformans. Brain or central nervous system (CNS) dissemination is the deadliest process for this disease; however, mechanisms underlying this process have yet to be elucidated. Moreover, illustrations of clinically relevant responses in cryptococcosis are currently limited due to the low availability of clinical samples. In this study, to explore the clinically relevant responses during C. neoformans infection, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feature of HIV/AIDS patients, was a centric pathway regulated in both infection models. Notably, assays of clinical immune cells confirmed an enhanced macrophage “Trojan Horse” in patients with HIV/AIDS, which could be shut down by cytoskeleton inhibitors. Furthermore, myocilin, encoded by MYOC, was found to be a novel enhancer for the macrophage “Trojan Horse,” and an enhanced fungal burden was achieved in the brains of MYOC-transgenic mice. Taken together, the findings from this study reveal fundamental roles of the cytoskeleton and MYOC in fungal CNS dissemination, which not only helps to understand the high prevalence of CM in HIV/AIDS but also facilitates the development of novel therapeutics for meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.
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影响因子：
6.4
作者：
Kogan, TV;Jadoun, J;Osherov, N
通讯作者：
Osherov, N
影响因子：
5.7
作者：
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通讯作者：
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DOI：
10.1038/s41579-021-00511-0
发表时间：
2021-07
期刊：
Nature reviews. Microbiology
影响因子：
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作者：
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通讯作者：
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影响因子：
5.5
作者：
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通讯作者：
Xu J
影响因子：
6.7
作者：
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通讯作者：
May, Robin C.