HTNV infection induces activation and deficiency of CD8+MAIT cells in HFRS patients

Author:

Zhang Yusi1ORCID,Wang Meng12,Zhang Xiyue13,Tang Kang1,Zhang Chunmei1,Jia Xiaozhou4,Hu Haifeng5,Liu He6,Li Na7,Zhuang Ran1,Jin Boquan1,Ma Ying1,Zhang Yun1

Affiliation:

1. Department of Immunology, School of Basic Medicine, Fourth Military Medical University , Xi’an 710032 , China

2. Department of Immunology, School of Basic Medical Sciences, Yan’an university , Yan’an 716000 , China

3. Department of Pathogenic Biology, School of Basic Medical Sciences, Yan’an university , Yan’an 716000 , China

4. Eighth Hospital of Xi’an , Xi’an 710061 , China

5. Center for Infectious Diseases, Second Affiliated Hospital of Air Force Medical University (Fourth Military Medical University) , Xi’an 710038 , China

6. Department of Microbiology, School of Basic Medicine, Fourth Military Medical University , Xi΄an 710032 , China

7. Department of Transfusion Medicine, Xijing Hospital, Fourth Military Medical University , Xi’an 710032, Shaanxi , China

Abstract

AbstractHantaan virus (HTNV) infection causes an epidemic of hemorrhagic fever with renal syndrome (HFRS) mainly in Asia. Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes known to play an important role in innate host defense during virus infection. However, their roles and phenotypes during HTNV infection have not yet been explored. We characterized CD8+MAIT cells from HFRS patients based on scRNA-seq data combined with flow cytometry data. We showed that HTNV infection caused the loss and activation of CD8+MAIT cells in the peripheral blood, which were correlated with disease severity. The production of granzyme B and IFN-γ from CD8+MAIT cells and the limitation of HTNV replication in endothelia cells indicated the anti-viral property of CD8+MAIT cells. In addition, in vitro infection of MAIT cells by HTNV or HTNV-exposed monocytes showed that the activation of MAIT cells was IL-18 mediated. In conclusion, this study identified, for the first time, gene expression profiles of MAIT cells, provided underlying molecular mechanisms for activation of MAIT cells during HTNV infection, and suggested a potential anti-viral role of MAIT cells in HFRS.

Funder

National Natural Science Foundation of China

Natural Science Basic Research Program of Shaanxi Province

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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