Details
- Autor(en) / Beteiligte
- Titel
- TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines
- Ist Teil von
- Nature immunology, 2021-07, Vol.22 (7), p.829
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The innate immune response is critical for recognizing and controlling infections through the release of cytokines and chemokines. However, severe pathology during some infections, including SARS-CoV-2, is driven by hyperactive cytokine release, or a cytokine storm. The innate sensors that activate production of proinflammatory cytokines and chemokines during COVID-19 remain poorly characterized. In the present study, we show that both TLR2 and MYD88 expression were associated with COVID-19 disease severity. Mechanistically, TLR2 and Myd88 were required for β-coronavirus-induced inflammatory responses, and TLR2-dependent signaling induced the production of proinflammatory cytokines during coronavirus infection independent of viral entry. TLR2 sensed the SARS-CoV-2 envelope protein as its ligand. In addition, blocking TLR2 signaling in vivo provided protection against the pathogenesis of SARS-CoV-2 infection. Overall, our study provides a critical understanding of the molecular mechanism of β-coronavirus sensing and inflammatory cytokine production, which opens new avenues for therapeutic strategies to counteract the ongoing COVID-19 pandemic.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1529-2916DOI: 10.1038/s41590-021-00937-xTitel-ID: cdi_pubmed_primary_33963333
- Format
- –
- Schlagworte
- Animals, Chlorocebus aethiops, Coronavirus Envelope Proteins - metabolism, COVID-19 - complications, COVID-19 - diagnosis, COVID-19 - drug therapy, COVID-19 - immunology, COVID-19 - virology, Cytokine Release Syndrome - diagnosis, Cytokine Release Syndrome - immunology, Cytokines - metabolism, Disease Models, Animal, Female, Gene Expression Profiling, Humans, Immunity, Innate - drug effects, Leukocytes, Mononuclear, Macrophages, Male, Mice, Mice, Knockout, Myeloid Differentiation Factor 88 - genetics, Myeloid Differentiation Factor 88 - metabolism, Primary Cell Culture, SARS-CoV-2 - immunology, SARS-CoV-2 - metabolism, SARS-CoV-2 - pathogenicity, Severity of Illness Index, Signal Transduction - drug effects, Signal Transduction - genetics, Signal Transduction - immunology, Toll-Like Receptor 2 - antagonists & inhibitors, Toll-Like Receptor 2 - genetics, Toll-Like Receptor 2 - metabolism, Vero Cells