TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection

Wu, Yongjian1,2,3,4,5,6; Wang, Manni1,2,3; Yin, Huan1,2,3; Ming, Siqi1,2,3,7; Li, Xingyu1,2,3; Jiang, Guanmin8; Liu, Ye1,2,3; Wang, Peihui9; Zhou, Guangde7; Liu, Lei7; Gong, Sitang5; Zhou, Haibo6; Shan, Hong1,2,3,4; Huang, Xi1,2,3,4,5,6,7

2021-12-01

10.1126/sciadv.abi6802

Science Advances   影响因子和分区

2375-2548

Limited understanding of T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has impeded vaccine development and drug discovery for coronavirus disease 2019 (COVID-19). We found that triggering receptor expressed on myeloid cells 2 (TREM-2) was induced in T cells in the blood and lungs of patients with COVID-19. After binding to SARS-CoV-2 membrane (M) protein through its immunoglobulin domain, TREM-2 then activated the CD3./ZAP70 complex, leading to STAT1 phosphorylation and T-bet transcription. In vitro stimulation with M protein-reconstituted pseudovirus or recombinant M protein, and TREM-2 promoted the T helper cell 1 (TH1) cytokines interferon-. and tumor necrosis factor. In vivo infection of CD4-TREM-2 conditional knockout mice with murine coronavirus mouse hepatitis virus A-59 showed that intrinsic TREM-2 in T cells enhanced TH1 response and viral clearance, thus aggravating lung destruction. These findings demonstrate a previously unidentified role for TREM-2 in SARS-CoV-2 infection, and suggest potential strategies for drug discovery and clinical management of COVID-19.

SCI ; EI

英语

NI论文

通讯

National Natural Science Foundation of China[82072062] ; National Science and Technology Key Projects for Major Infectious Diseases[2017ZX10302301-002] ; Guangzhou Science and Technology Planning Project[201704020226,201604020006] ; National Key Research and Development Program of China[2016YFC1200105] ; Three Major Scientific Research Projects of Sun Yatsen University[20200326236] ; Guangdong Scientific and Technological Research Project for COVID-19 containment["2020A111128022","2020B111112003"] ; Guangdong Scientific and Technological Research for COVID-19[202020012612200001] ; Zhuhai Scientific and Technological Research Project for COVID-19 containment[ZH22036302200029PWC]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000728174000009

AMER ASSOC ADVANCEMENT SCIENCE

20215011318203

Cell death ; Glycoproteins ; Mammals ; Recombinant proteins ; T-cells

Medicine and Pharmacology:461.6 ; Biology:461.9 ; Immunology:461.9.1 ; Organic Compounds:804.1

Web of Science

1.Sun Yat Sen Univ, Affiliated Hosp 5, Ctr Infect & Immun, Zhuhai 519000, Guangdong, Peoples R China
2.Sun Yat Sen Univ, Affiliated Hosp 5, Guangdong Prov Engn Res Ctr Mol Imaging, Guangdong Prov Key Lab Biomed Imaging, Zhuhai 519000, Guangdong, Peoples R China
3.Sun Yat Sen Univ, Affiliated Hosp 5, Dept Intervent Med, Zhuhai 519000, Guangdong, Peoples R China
4.Southern Marine Sci & Engn Guangdong Lab, Zhuhai 519000, Guangdong, Peoples R China
5.Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangzhou Inst Pediat, Dept Gastroenterol, Guangzhou 510623, Guangdong, Peoples R China
6.Guangzhou Med Univ, Qingyuan Peoples Hosp, Affiliated Hosp 6, Qingyuan 511518, Guangdong, Peoples R China
7.Southern Univ Sci & Technol, Shenzhen Third Peoples Hosp, Natl Clin Res Ctr Infect Dis, Affiliated Hosp 2, Shenzhen 518112, Guangdong, Peoples R China
8.Sun Yat Sen Univ, Dept Clin Lab, Affiliated Hosp 5, Zhuhai 519000, Guangdong, Peoples R China
9.Shandong Univ, Cheeloo Coll Med, Adv Med Res Inst, Jinan 250012, Shandong, Peoples R China

Wu, Yongjian,Wang, Manni,Yin, Huan,et al. TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection[J]. Science Advances,2021,7(50).

Wu, Yongjian.,Wang, Manni.,Yin, Huan.,Ming, Siqi.,Li, Xingyu.,...&Huang, Xi.(2021).TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection.Science Advances,7(50).

Wu, Yongjian,et al."TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection".Science Advances 7.50(2021).