Alveolar type II (ATII) pneumocytes as defenders of the alveolus are critical to repairing lung injury. We investigated the ATII reparative response in COVID-19 pneumonia, because the initial proliferation of ATII cells in this reparative process should provide large numbers of target cells to amplify SARS-CoV-2 virus production and cytopathological effects to compromise lung repair. We show that both infected and uninfected ATII cells succumb to tumor necrosis factor-α (TNF)-induced necroptosis, Bruton's tyrosine kinase (BTK)-induced pyroptosis and a new PANoptotic hybrid form of inflammatory cell death mediated by a PANoptosomal latticework that generates distinctive COVID-19 pathologies in contiguous ATII cells. Identifying TNF and BTK as the initiators of programmed cell death and SARS-CoV-2 cytopathic effects provides a rationale for early antiviral treatment combined with inhibitors of TNF and BTK to preserve ATII cell populations, reduce programmed cell death and associated hyperinflammation, and restore functioning alveoli in COVID-19 pneumonia.

The Defenders of the Alveolus Succumb in COVID-19 Pneumonia to SARS-CoV-2 and Necroptosis, Pyroptosis and Panoptosis / L. Schifanella, J. Anderson, G. Wieking, P. J Southern, S. Antinori, M. Galli, M. Corbellino, A. Lai, N. Klatt, T. W Schacker, A. T Haase. - In: THE JOURNAL OF INFECTIOUS DISEASES. - ISSN 0022-1899. - (2023), pp. jiad056.1-jiad056.9. [Epub ahead of print] [10.1093/infdis/jiad056]

The Defenders of the Alveolus Succumb in COVID-19 Pneumonia to SARS-CoV-2 and Necroptosis, Pyroptosis and Panoptosis

L. Schifanella
Primo
Writing – Original Draft Preparation
;
S. Antinori;M. Galli;A. Lai;
2023

Abstract

Alveolar type II (ATII) pneumocytes as defenders of the alveolus are critical to repairing lung injury. We investigated the ATII reparative response in COVID-19 pneumonia, because the initial proliferation of ATII cells in this reparative process should provide large numbers of target cells to amplify SARS-CoV-2 virus production and cytopathological effects to compromise lung repair. We show that both infected and uninfected ATII cells succumb to tumor necrosis factor-α (TNF)-induced necroptosis, Bruton's tyrosine kinase (BTK)-induced pyroptosis and a new PANoptotic hybrid form of inflammatory cell death mediated by a PANoptosomal latticework that generates distinctive COVID-19 pathologies in contiguous ATII cells. Identifying TNF and BTK as the initiators of programmed cell death and SARS-CoV-2 cytopathic effects provides a rationale for early antiviral treatment combined with inhibitors of TNF and BTK to preserve ATII cell populations, reduce programmed cell death and associated hyperinflammation, and restore functioning alveoli in COVID-19 pneumonia.
BTK; COVID-19 pneumonia; SARS-CoV-2; TNF; Type II pneumocytes; lung repair; necroptosis; panoptosis; pyroptosis
Settore MED/17 - Malattie Infettive
Settore MED/42 - Igiene Generale e Applicata
Settore MED/08 - Anatomia Patologica
Settore MED/07 - Microbiologia e Microbiologia Clinica
2023
3-mar-2023
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/956978
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