Single-cell sequencing resolves the landscape of immune cells and regulatory mechanisms in HIV-infected immune non-responders

Autor: Haiyu Li, Yongyao Tang, Yujing Wang, Yue Li, Yi Yang, Kui Liao, Fangzhou Song, Shixiong Deng, Yaokai Chen
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cell Death and Disease, Vol 13, Iss 10, Pp 1-12 (2022)
Druh dokumentu: article
ISSN: 2041-4889
DOI: 10.1038/s41419-022-05225-6
Popis: Abstract 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.
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