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TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection
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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654301/ https://www.ncbi.nlm.nih.gov/pubmed/34878838 http://dx.doi.org/10.1126/sciadv.abi6802 |
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author | Wu, Yongjian Wang, Manni Yin, Huan Ming, Siqi Li, Xingyu Jiang, Guanmin Liu, Ye Wang, Peihui Zhou, Guangde Liu, Lei Gong, Sitang Zhou, Haibo Shan, Hong Huang, Xi |
author_facet | Wu, Yongjian Wang, Manni Yin, Huan Ming, Siqi Li, Xingyu Jiang, Guanmin Liu, Ye Wang, Peihui Zhou, Guangde Liu, Lei Gong, Sitang Zhou, Haibo Shan, Hong Huang, Xi |
author_sort | Wu, Yongjian |
collection | PubMed |
description | 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(H)1) 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(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. |
format | Online Article Text |
id | pubmed-8654301 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-86543012021-12-16 TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection Wu, Yongjian Wang, Manni Yin, Huan Ming, Siqi Li, Xingyu Jiang, Guanmin Liu, Ye Wang, Peihui Zhou, Guangde Liu, Lei Gong, Sitang Zhou, Haibo Shan, Hong Huang, Xi Sci Adv Biomedicine and Life Sciences 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(H)1) 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(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. American Association for the Advancement of Science 2021-12-08 /pmc/articles/PMC8654301/ /pubmed/34878838 http://dx.doi.org/10.1126/sciadv.abi6802 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Wu, Yongjian Wang, Manni Yin, Huan Ming, Siqi Li, Xingyu Jiang, Guanmin Liu, Ye Wang, Peihui Zhou, Guangde Liu, Lei Gong, Sitang Zhou, Haibo Shan, Hong Huang, Xi TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection |
title | TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection |
title_full | TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection |
title_fullStr | TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection |
title_full_unstemmed | TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection |
title_short | TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection |
title_sort | trem-2 is a sensor and activator of t cell response in sars-cov-2 infection |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654301/ https://www.ncbi.nlm.nih.gov/pubmed/34878838 http://dx.doi.org/10.1126/sciadv.abi6802 |
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