Single-cell Sequencing Resolves Landscape of Immune cell and Regulatory Mechanisms in HIV-infected immune non-responders

Immune non-responder (INR) after highly active antiretroviral therapy (HAART) is the main cause of opportunistic infection 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 nonresponder (INR) and responder (IR) HIV-1-infected subjects. We then describe the mitochondrial function of MAIT by flow cytometry in INRs and IRs. We founded there were diminished frequencies and numbers of MAIT cells in INRs, and MAIT cells from INRs displayed transcriptional profiles associated with the impairment of mitochondrial function and apoptosis signaling. 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 PPARA. These findings demonstrate the restoring mitochondrial function could modulate the immune dysfunction characteristic of MAIT, which against bacterial co-infections in INRs subjects.