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

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 (TH1) 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 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.

• 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
• Journal: Science advances (Sci Adv) Vol. 7 Issue 50 Pg. eabi6802 (Dec 10 2021) ISSN: 2375-2548 [Electronic] United States
• PMID: 34878838 (Publication Type: Journal Article)