SARS-CoV-2 envelope protein regulates innate immune tolerance.
| Autor: | Geanes ES; Genomic Medicine Center, Children's Mercy Research Institute, Kansas City, MO, USA., McLennan R; Genomic Medicine Center, Children's Mercy Research Institute, Kansas City, MO, USA., Pierce SH; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA., Menden HL; Division of Neonatology, Children's Mercy Research Institute, Kansas City, MO, USA., Paul O; Genomic Medicine Center, Children's Mercy Research Institute, Kansas City, MO, USA., Sampath V; Division of Neonatology, Children's Mercy Research Institute, Kansas City, MO, USA.; Department of Pediatrics, University of Missouri- Kansas City, Kansas City, MO, USA., Bradley T; Genomic Medicine Center, Children's Mercy Research Institute, Kansas City, MO, USA.; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.; Department of Pediatrics, University of Missouri- Kansas City, Kansas City, MO, USA.; Department of Pediatrics, University of Kansas Medical Center, Kansas City, MO, USA. |
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| Jazyk: | angličtina |
| Zdroj: | IScience [iScience] 2024 May 15; Vol. 27 (6), pp. 109975. Date of Electronic Publication: 2024 May 15 (Print Publication: 2024). |
| DOI: | 10.1016/j.isci.2024.109975 |
| Abstrakt: | Severe COVID-19 often leads to secondary infections and sepsis that contribute to long hospital stays and mortality. However, our understanding of the precise immune mechanisms driving severe complications after SARS-CoV-2 infection remains incompletely understood. Here, we provide evidence that the SARS-CoV-2 envelope (E) protein initiates innate immune inflammation, via toll-like receptor 2 signaling, and establishes a sustained state of innate immune tolerance following initial activation. Monocytes in this tolerant state exhibit reduced responsiveness to secondary stimuli, releasing lower levels of cytokines and chemokines. Mice exposed to E protein before secondary lipopolysaccharide challenge show diminished pro-inflammatory cytokine expression in the lung, indicating that E protein drives this tolerant state in vivo . These findings highlight the potential of the SARS-CoV-2 E protein to induce innate immune tolerance, contributing to long-term immune dysfunction that could lead to susceptibility to subsequent infections, and uncovers therapeutic targets aimed at restoring immune function following SARS-CoV-2 infection. Competing Interests: The authors declare no competing interests. (© 2024 The Author(s).) |
| Databáze: | MEDLINE |
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