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

Peng Xia; Xu-Dong Xing; Cui-Xian Yang; Xue-Jiao Liao; Fu-Hua Liu; Hui-Huang Huang; Chao Zhang; Jin-Wen Song; Yan-Mei Jiao; Ming Shi; Tian-Jun Jiang; Chun-Bao Zhou; Xi-Cheng Wang; Qing He; Qing-Lei Zeng; Fu-Sheng Wang; Ji-Yuan Zhang

doi:10.1186/s40779-022-00384-1

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

RESEARCH | Updated：2023-03-23

- Activation-induced pyroptosis contributes to the loss of MAIT cells in chronic HIV-1 infected patients
- Military Medical Research Vol. 10, Issue 1, Pages: 45-63(2023)
- Affiliations：
  
  1.Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100039 , China
  2.Department of Infectious Diseases and Hepatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 , China
  3.Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871 , China
  4.Yunnan Infectious Disease Hospital, Kunming 650301, China
  5.The Third People’s Hospital of Shenzhen, School of Medicine, Southern University of Science and Technology, Shenzhen 518112 , Guangzhou, China
- Author bio：
  
  * zengqinglei2009@163.com;
  fswang302@163.com;
  uniquezjy@163.com
- Funds：
- DOI：10.1186/s40779-022-00384-1
  CLC：
- Published：2023-02
- Accepted：
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Xia P, Xing XD, Yang CX, Liao XJ, Liu FH, Huang HH, et al. Activation-induced pyroptosis contributes to the loss of MAIT cells in chronic HIV-1 infected patients. Mil Med Res. 2022;9(1):24.
DOI：

Xia P, Xing XD, Yang CX, Liao XJ, Liu FH, Huang HH, et al. Activation-induced pyroptosis contributes to the loss of MAIT cells in chronic HIV-1 infected patients. Mil Med Res. 2022;9(1):24. DOI： 10.1186/s40779-022-00384-1.

摘要

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.

关键词

Keywords

references

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