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Comment
. 2022 Jan 31;7(1):32.
doi: 10.1038/s41392-022-00892-5.

NK cell dysfunction in severe COVID-19: TGF-β-induced downregulation of integrin beta-2 restricts NK cell cytotoxicity

Joana Barros-Martins  1 , Reinhold Förster  1   2   3 , Berislav Bošnjak  4
Affiliations
Comment

NK cell dysfunction in severe COVID-19: TGF-β-induced downregulation of integrin beta-2 restricts NK cell cytotoxicity

Joana Barros-Martins et al. Signal Transduct Target Ther. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Production of tumor growth factor-beta (TGF-β) inhibits the antiviral functions of NK cells in response to SARS-CoV-2 infection. In severe but not in moderate COVID-19 patients, the high TGF-β concentration might be a result of SARS-CoV-2 infection (depicted) and/or co-morbidities. In severe COVID-19 patients, TGF-β is produced by various cell types, including type 1 alveolar epithelial cells (depicted), fibroblasts, myofibroblasts, and myeloid cells. TGF-β counteracts interferon-alpha (IFN-α)-induced activation of recruited natural killer (NK) cells, impedes T-bet activation, and skews the transcription activity towards Eomes. Consequently, these cells have lower expression of integrin-β2 (CD18), IFN-gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). Lack of integrin-β2 molecules precludes firm adhesion of NK cells to infected cells, preventing NK cell degranulation and killing of infected cells, thus leading to uncontrolled virus spread
See this image and copyright information in PMC

Comment on

  • Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells.
    Witkowski M, Tizian C, Ferreira-Gomes M, Niemeyer D, Jones TC, Heinrich F, Frischbutter S, Angermair S, Hohnstein T, Mattiola I, Nawrath P, McEwen S, Zocche S, Viviano E, Heinz GA, Maurer M, Kölsch U, Chua RL, Aschman T, Meisel C, Radke J, Sawitzki B, Roehmel J, Allers K, Moos V, Schneider T, Hanitsch L, Mall MA, Conrad C, Radbruch H, Duerr CU, Trapani JA, Marcenaro E, Kallinich T, Corman VM, Kurth F, Sander LE, Drosten C, Treskatsch S, Durek P, Kruglov A, Radbruch A, Mashreghi MF, Diefenbach A. Witkowski M, et al. Nature. 2021 Dec;600(7888):295-301. doi: 10.1038/s41586-021-04142-6. Epub 2021 Oct 25. Nature. 2021. PMID: 34695836

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