1. Activation-induced pyroptosis contributes to the loss of MAIT cells in chronic HIV-1 infected patients.
- Author
-
Xia, Peng, Xing, Xu-Dong, Yang, Cui-Xian, Liao, Xue-Jiao, Liu, Fu-Hua, Huang, Hui-Huang, Zhang, Chao, Song, Jin-Wen, Jiao, Yan-Mei, Shi, Ming, Jiang, Tian-Jun, Zhou, Chun-Bao, Wang, Xi-Cheng, He, Qing, Zeng, Qing-Lei, Wang, Fu-Sheng, and Zhang, Ji-Yuan
- Subjects
AIDS ,PYROPTOSIS ,HIV ,LONG-term non-progressors ,IMMUNOSTAINING - 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 cytokines interleukin-12 (IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro. Conclusions: Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients, which could potentiate disease progression and poor immune reconstitution. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF