Single-cell sequencing resolves the landscape of immune cells and regulatory mechanisms in HIV-infected immune non-responders.
Single-cell sequencing resolves the landscape of immune cells and regulatory mechanisms in HIV-infected immune non-responders.
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DOI：
10.1038/s41419-022-05225-6
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发表时间：
2022-10-04
影响因子：
9
通讯作者：
Chen, Yaokai
中科院分区：
文献类型：
--
作者：
Li, Haiyu;Tang, Yongyao;Wang, Yujing;Li, Yue;Yang, Yi;Liao, Kui;Song, Fangzhou;Deng, Shixiong;Chen, Yaokai
高效抗逆转录病毒治疗（HAART）后的免疫无应答是艾滋病患者机会性感染和高死亡率的主要原因，但免疫重建失败的机制尚不清楚。在这里，我们对来自免疫无应答者（INR）和应答者（IR）HIV-1感染受试者的外周血单核细胞（PBMC）进行了scRNA-seq和scATAC-seq分析。我们发现在INR中粘膜相关不变T（MAIT）细胞的低表达，其表现出与受损的线粒体功能和凋亡信号相关的转录谱。转座酶可接近染色质的单细胞测定（scATAC-seq）和流式细胞术揭示了来自INR的MAIT细胞中线粒体适应性降低，并且MAIT具有线粒体转录因子A（TFAM）和过氧化物酶体增殖物激活受体α（PPARA）的低表达。这些发现表明，恢复线粒体功能可以调节MAIT针对INR受试者中细菌合并感染的免疫功能障碍特征。
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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线粒体 PKM2 通过稳定 Bcl2 来调节氧化应激诱导的细胞凋亡。
影响因子：
44.1
作者：
Liang J;Cao R;Wang X;Zhang Y;Wang P;Gao H;Li C;Yang F;Zeng R;Wei P;Li D;Li W;Yang W
通讯作者：
Yang W
影响因子：
30.5
作者：
Le Bourhis, Lionel;Martin, Emmanuel;Lantz, Olivier
通讯作者：
Lantz, Olivier
影响因子：
82.9
作者：
Ahuja, Sunil K.;Kulkarni, Hemant;Dolan, Matthew J.
通讯作者：
Dolan, Matthew J.
影响因子：
30.5
作者：
Awad, Wael;Ler, Geraldine J. M.;Rossjohn, Jamie
通讯作者：
Rossjohn, Jamie
DOI：
10.15585/mmwr.mm6912a3
发表时间：
2020-03-27
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
Melgar M;Nichols C;Cavanaugh JS;Kirking HL;Surie D;Date A;Ahmedov S;Maloney S;Fukunaga R;CDC Country Offices’ Tuberculosis/HIV Advisors;National Ministries and Departments of Health Tuberculosis Program Managers
通讯作者：
National Ministries and Departments of Health Tuberculosis Program Managers