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

• Published in: Cell death & disease Vol. 13; no. 10; p. 849
• Main Authors: Li, Haiyu, Tang, Yongyao, Wang, Yujing, Li, Yue, Yang, Yi, Liao, Kui, Song, Fangzhou, Deng, Shixiong, Chen, Yaokai
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.10.2022; Springer Nature B.V; Nature Publishing Group
• Subjects: 45/15; 45/22; 45/23; 45/41; 45/61; 45/77; 631/80/83/2360; 692/699/255/1901; Acquired immune deficiency syndrome; AIDS; Antibodies; Apoptosis; Biochemistry; Biomedical and Life Sciences; Blood & organ donations; Cell Biology; Cell Culture; Chromatin; Drug therapy; E coli; Flow cytometry; Gene expression; Genomics; Highly active antiretroviral therapy; HIV; HIV Infections - drug therapy; HIV Infections - genetics; Human immunodeficiency virus; Humans; Immune reconstitution; Immune system; Immunology; Infections; Infectious diseases; Leukocytes, Mononuclear; Life Sciences; Lymphocytes; Mitochondria; Mortality; Mucosa; Peripheral blood mononuclear cells; Transcription Factors; Transposase; Transposases
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-022-05225-6

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.