tetano
Editor, Senior Moderator
Nat Immunol
. 2021 May 7.
doi: 10.1038/s41590-021-00937-x. Online ahead of print.
TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines
Min Zheng[SUP] 1 [/SUP], Rajendra Karki[SUP] 1 [/SUP], Evan Peter Williams[SUP] 2 [/SUP], Dong Yang[SUP] 3 [/SUP], Elizabeth Fitzpatrick[SUP] 3 [/SUP], Peter Vogel[SUP] 4 [/SUP], Colleen Beth Jonsson[SUP] 2 [/SUP], Thirumala-Devi Kanneganti[SUP] 5 [/SUP]
Affiliations
Abstract
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 ?-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 ?-coronavirus sensing and inflammatory cytokine production, which opens new avenues for therapeutic strategies to counteract the ongoing COVID-19 pandemic.
. 2021 May 7.
doi: 10.1038/s41590-021-00937-x. Online ahead of print.
TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines
Min Zheng[SUP] 1 [/SUP], Rajendra Karki[SUP] 1 [/SUP], Evan Peter Williams[SUP] 2 [/SUP], Dong Yang[SUP] 3 [/SUP], Elizabeth Fitzpatrick[SUP] 3 [/SUP], Peter Vogel[SUP] 4 [/SUP], Colleen Beth Jonsson[SUP] 2 [/SUP], Thirumala-Devi Kanneganti[SUP] 5 [/SUP]
Affiliations
- PMID: 33963333
- DOI: 10.1038/s41590-021-00937-x
Abstract
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 ?-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 ?-coronavirus sensing and inflammatory cytokine production, which opens new avenues for therapeutic strategies to counteract the ongoing COVID-19 pandemic.