Activation-induced pyroptosis contributes to the loss of MAIT cells in chronic HIV-1 infected patients

作者：Peng Xia, Xudong Xing, Cuixian Yang, Xuejiao Liao, Fuhua Liu, Hui-Huang Huang, Chao Zhang, Jin‐Wen Song, Yan‐Mei Jiao, Ming Shi, Tianjun Jiang, Chun‐Bao Zhou, Xicheng Wang, Qing He, Qing‐Lei Zeng, Fu‐Sheng Wang, Ji‐Yuan Zhang · 发表于：Military Medical Research · 年份：2022 · DOI：10.1186/s40779-022-00384-1 · 被引用次数：35 · 研究领域：Immune Cell Function and Interaction、Inflammasome and immune disorders、Autoimmune and Inflammatory Disorders Research

Abstract Background Mucosal-associated invariant T (MAIT) cells are systemically depleted in human immunodeficiency virus type 1 (HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy (cART). This study aimed to identify the mechanism underlying MAIT cell depletion. Methods In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. Results Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4 + T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D (GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory ...