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

• DOI: 10.1126/sciadv.abi6802
• Publication Date: 2021-12-08T18:55:18Z
• Authors: 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
• Keywords: STAT1; Coronavirus

Limited understanding of T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has impeded vaccine development and drug discovery for disease 2019 (COVID-19). We found that triggering receptor expressed on myeloid cells (TREM-2) was induced in the blood lungs patients with COVID-19. After binding to SARS-CoV-2 membrane (M) protein through its immunoglobulin domain, TREM-2 then activated CD3ζ/ZAP70 complex, leading STAT1 phosphorylation T-bet transcription. In vitro stimulation M protein-reconstituted pseudovirus or recombinant protein, promoted helper 1 (TH1) cytokines interferon-γ tumor necrosis factor. vivo infection CD4–TREM-2 conditional knockout mice murine mouse hepatitis virus A-59 showed intrinsic enhanced TH1 response viral clearance, thus aggravating lung destruction. These findings demonstrate a previously unidentified role infection, suggest potential strategies clinical management