| First Author | Wu Y | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 50 | Pages | eabi6802 |
| PubMed ID | 34878838 | Mgi Jnum | J:320018 |
| Mgi Id | MGI:6836537 | Doi | 10.1126/sciadv.abi6802 |
| Citation | Wu Y, et al. (2021) TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection. Sci Adv 7(50):eabi6802 |
| abstractText | 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 CD3zeta/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(H)1) cytokines interferon-gamma 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(H)1 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. |
