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

Yongjian Wu; Manni Wang; Huan Yin; Siqi Ming; Xingyu Li; Guanmin Jiang; Ye Liu; Peihui Wang; Guangde Zhou; Lei Liu; Sitang Gong; Haibo Zhou; Hong Shan; Xi Huang

doi:10.1126/sciadv.abi6802

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

Sci Adv. 2021 Dec 10;7(50):eabi6802. doi: 10.1126/sciadv.abi6802. Epub 2021 Dec 8.

Authors

Yongjian Wu^{1

2

3

4

5}, Manni Wang^{1

2}, Huan Yin^{1

2}, Siqi Ming^{1

2

6}, Xingyu Li^{1

2}, Guanmin Jiang⁷, Ye Liu^{1

2}, Peihui Wang⁸, Guangde Zhou⁶, Lei Liu⁶, Sitang Gong⁴, Haibo Zhou⁵, Hong Shan^{1

2

3}, Xi Huang^{1

2

3

4

5

6}

Affiliations

¹ Center for Infection and Immunity, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China.
² Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong Provincial Key Laboratory of Biomedical Imaging, and Department of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China.
³ Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, Guangdong Province 519000, China.
⁴ Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Institute of Pediatrics, Guangzhou Medical University, Guangzhou, Guangdong Province 510623, China.
⁵ The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong Province 511518, China.
⁶ National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong Province 518112, China.
⁷ Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China.
⁸ Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province 250012, China.

Abstract

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 CD3ζ/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 (T_H1) cytokines interferon-γ 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 T_H1 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.