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- Title
Activation-induced pyroptosis contributes to the loss of MAIT cells in chronic HIV-1 infected patients.
- Authors
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; Zhang, Ji-Yuan
- 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.
- Subjects
BEIJING (China); AIDS; PYROPTOSIS; HIV; LONG-term non-progressors; IMMUNOSTAINING
- Publication
Military Medical Research, 2022, Vol 9, Issue 1, p1
- ISSN
2095-7467
- Publication type
Article
- DOI
10.1186/s40779-022-00384-1