Comparative miRNA transcriptomics of macaques and mice reveals MYOC is an inhibitor for Cryptococcus neoformans invasion into the brain
Year: 2022
Type: dataset
Abstract: 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.
Source: Figshare
Authors: Li, Hailong, Han, Xiaoxu, Du, Wei, Meng, Yang, Li, Yanjian, Sun, Tianshu, Liang, Qiaojing, Li, Chao, Suo, Chenhao, Gao, Xindi, Qiu, Yu, Tian, Wen, An, Minghui, Zhang, Hui, Fu, Yajing, Li, Xiaolin, Lan, Tian, Yang, Sheng, Zhang, Zining, Geng, Wenqing, Ding, Chen, Shang, Hong
Institutions: Yanbian University, Affiliated Hospital of Qingdao University, First Hospital of China Medical University, Zhejiang University, Chongqing University of Posts and Telecommunications, Chinese Academy of Medical Sciences & Peking Union Medical College, Southeast University, Sichuan University, First Affiliated Hospital of Zhengzhou University, Jiangnan University, Tianjin University of Science and Technology, East China University of Science and Technology, Third Hospital of Hebei Medical University, Institute of Acoustics, Soil and Fertilizer Institute of Hunan Province, Guangdong Provincial People's Hospital, Shandong First Medical University, University of Chinese Academy of Sciences, Hangzhou Medical College, Xi'an Jiaotong University, Chongqing Medical University, Chinese PLA General Hospital, Beijing Jishuitan Hospital, Shanghai University, Tongji University, Yunnan Normal University, Montefiore Medical Center, Guangdong University of Technology, Johns Hopkins University, Xinjiang Medical University, Harbin Medical University, Sun Yat-sen University, Northeast Agricultural University, Guizhou University, Chinese Center For Disease Control and Prevention, Chinese Academy of Sciences, Huazhong Agricultural University, Fudan University, First Affiliated Hospital of Xinjiang Medical University, Jiangsu Academy of Agricultural Sciences, Peking University People's Hospital, First Hospital of Shanxi Medical University, First Affiliated Hospital of GuangXi Medical University, Second Hospital of Shanxi Medical University, Beijing Academy of Agriculture and Forestry Sciences, Huashan Hospital, University College London, Yangzhou University, Jinzhou Medical University, Guangzhou Medical University, University Hospital Münster, Shanghai Sixth People's Hospital, Jiangsu Province Hospital, Anhui Agricultural University, Shandong University, Second Affiliated Hospital of Nanchang University, Hangzhou Hospital of Traditional Chinese Medicine, Fujian Agriculture and Forestry University, Nanjing Medical University, Central South University, Zhengzhou University, Henan Normal University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4394094365