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

作者全名:"Li, Haiyu; Tang, Yongyao; Wang, Yujing; Li, Yue; Yang, Yi; Liao, Kui; Song, Fangzhou; Deng, Shixiong; Chen, Yaokai"

作者地址:"[Li, Haiyu; Chen, Yaokai] Chongqing Publ Hlth Med Ctr, Dept Infect Dis, Chongqing 400036, Peoples R China; [Li, Haiyu] Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Chongqing 400714, Peoples R China; [Tang, Yongyao; Wang, Yujing] Chongqing Med Univ, Sch Med Informat, Chongqing 400016, Peoples R China; [Li, Yue; Song, Fangzhou; Deng, Shixiong] Chongqing Med Univ, Basic Med Coll, Chongqing 400016, Peoples R China; [Yang, Yi] Chongqing Med Univ, Clin Coll 1, Chongqing 400016, Peoples R China; [Liao, Kui] Chongqing Med Univ, Affiliated Hosp 1, Dept Radiotherapy, Chongqing 400016, Peoples R China"

通信作者:"Chen, YK (通讯作者),Chongqing Publ Hlth Med Ctr, Dept Infect Dis, Chongqing 400036, Peoples R China.; Song, FZ; Deng, SX (通讯作者),Chongqing Med Univ, Basic Med Coll, Chongqing 400016, Peoples R China.; Liao, K (通讯作者),Chongqing Med Univ, Affiliated Hosp 1, Dept Radiotherapy, Chongqing 400016, Peoples R China."

来源:CELL DEATH & DISEASE

ESI学科分类:MOLECULAR BIOLOGY & GENETICS

WOS号:WOS:000863842300002

JCR分区:Q1

影响因子:9

年份:2022

卷号:13

期号:10

开始页: 

结束页: 

文献类型:Article

关键词: 

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."

基金机构:"National Natural Science Foundation of China [82002154]; National Science and Technology Major Project of China during the 13th Five-year plan period [2018ZX10302104]; General Project of Chongqing Basic Research and Frontier Exploration Project (Natural Science Foundation), China [cstc2019jcyj-msxmX0029]"

基金资助正文:"This work was supported by the National Natural Science Foundation of China [No. 82002154], National Science and Technology Major Project of China during the 13th Five-year plan period [No. 2018ZX10302104] and the General Project of Chongqing Basic Research and Frontier Exploration Project (Natural Science Foundation), China [No. cstc2019jcyj-msxmX0029]."