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

Xia, Peng1,2; Xing, Xu-Dong3; Yang, Cui-Xian4; Liao, Xue-Jiao5; Liu, Fu-Hua1,2; Huang, Hui-Huang1; Zhang, Chao1; Song, Jin-Wen1; Jiao, Yan-Mei1; Shi, Ming1; Jiang, Tian-Jun1; Zhou, Chun-Bao1; Wang, Xi-Cheng4; He, Qing5; Zeng, Qing-Lei2; Wang, Fu-Sheng1; Zhang, Ji-Yuan1

2022-05-27

10.1186/s40779-022-00384-1

Military Medical Research   影响因子和分区

2095-7467

2054-9369

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.

Acquired immune deficiency syndrome Human immunodeficiency virus Mucosal-associated invariant T cells Pyroptosis Immune reconstitution

SCI

英语

其他

Peking University Clinical Scientist Program Special[BMU2019LCKXJ013] ; National Natural Science Foundation Innovation Research Group Project[81721002] ; Sanming Project of Medicine Project in Shenzhen[SZSM201612014] ; Kunming Medical University[202001AY070001-154] ; Scientific Research Fund of Education Department of Yunnan Province[2021J0297]

General & Internal Medicine

Medicine, General & Internal

WOS:000805596200001

BMC

2-s2.0-85130763991

Web of Science

1.Univ Chinese Acad Sci, Chinese PLA Gen Hosp, Med Ctr 5, Natl Clin Res Ctr Infect Dis,Savaid Med Sch,Senio, Beijing 100039, Peoples R China
2.Zhengzhou Univ, Affiliated Hosp 1, Dept Infect Dis & Hepatol, Zhengzhou 450052, Peoples R China
3.Peking Univ, Biomed Pioneering Innovat Ctr BIOPIC, Sch Life Sci, Beijing 100871, Peoples R China
4.Yunnan Infect Dis Hosp, Kunming 650301, Yunnan, Peoples R China
5.Southern Univ Sci & Technol, Peoples Hosp Shenzhen 3, Sch Med, Guangzhou 518112, Peoples R China

Xia, Peng,Xing, Xu-Dong,Yang, Cui-Xian,et al. Activation-induced pyroptosis contributes to the loss of MAIT cells in chronic HIV-1 infected patients[J]. Military Medical Research,2022,9(1).

Xia, Peng.,Xing, Xu-Dong.,Yang, Cui-Xian.,Liao, Xue-Jiao.,Liu, Fu-Hua.,...&Zhang, Ji-Yuan.(2022).Activation-induced pyroptosis contributes to the loss of MAIT cells in chronic HIV-1 infected patients.Military Medical Research,9(1).

Xia, Peng,et al."Activation-induced pyroptosis contributes to the loss of MAIT cells in chronic HIV-1 infected patients".Military Medical Research 9.1(2022).