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Single-cell sequencing resolves the landscape of immune cells and regulatory mechanisms in HIV-infected immune non-responders
Li, Haiyu1,2; Tang, Yongyao3; Wang, Yujing3; Li, Yue4; Yang, Yi5; Liao, Kui6; Song, Fangzhou4; Deng, Shixiong4; Chen, Yaokai1
2022-10-04
摘要Immune non-responder after highly active antiretroviral therapy (HAART) is the main cause of opportunistic infections and high mortality in AIDS patients, but the mechanism underlying immune reconstitution failure is poorly understood. Here, we performed scRNA-seq, and scATAC-seq analysis of peripheral blood mononuclear cells (PBMCs) derived from immune non-responder (INR) and responder (IR) HIV-1-infected subjects. We found low expression of mucosal-associated invariant T (MAIT) cells in INRs, which exhibited transcriptional profiles associated with impaired mitochondrial function and apoptosis signaling. Single-cell assays for transposase-accessible chromatin (scATAC-seq) and flow cytometry revealed diminished mitochondrial fitness in MAIT cells from INRs, and MAIT had low expression of transcription factor A for mitochondria (TFAM) and peroxisomal proliferator-activated receptor alpha (PPARA). These findings demonstrate that restoring mitochondrial function could modulate the immune dysfunction characteristic of MAIT against bacterial co-infections in INRs subjects.
DOI10.1038/s41419-022-05225-6
发表期刊CELL DEATH & DISEASE
ISSN2041-4889
卷号13期号:10页码:12
通讯作者Liao, Kui(klcqmu@163.com) ; Song, Fangzhou(fzsongcq@163.com) ; Deng, Shixiong(dengshixiong1963@163.com) ; Chen, Yaokai(ykchencmc@163.com)
收录类别SCI
WOS记录号WOS:000863842300002
语种英语