tetano
Editor, Senior Moderator
Cell
. 2021 Aug 19;S0092-8674(21)00990-9.
doi: 10.1016/j.cell.2021.08.016. Online ahead of print.
The interferon landscape along the respiratory tract impacts the severity of COVID-19
Benedetta Sposito[SUP] 1 [/SUP], Achille Broggi[SUP] 2 [/SUP], Laura Pandolfi[SUP] 3 [/SUP], Stefania Crotta[SUP] 4 [/SUP], Nicola Clementi[SUP] 5 [/SUP], Roberto Ferrarese[SUP] 6 [/SUP], Sofia Sisti[SUP] 6 [/SUP], Elena Criscuolo[SUP] 6 [/SUP], Roberto Spreafico[SUP] 7 [/SUP], Jaclyn M Long[SUP] 8 [/SUP], Alessandro Ambrosi[SUP] 9 [/SUP], Enju Liu[SUP] 10 [/SUP], Vanessa Frangipane[SUP] 3 [/SUP], Laura Saracino[SUP] 3 [/SUP], Sara Bozzini[SUP] 3 [/SUP], Laura Marongiu[SUP] 11 [/SUP], Fabio A Facchini[SUP] 11 [/SUP], Andrea Bottazzi[SUP] 12 [/SUP], Tommaso Fossali[SUP] 13 [/SUP], Riccardo Colombo[SUP] 13 [/SUP], Massimo Clementi[SUP] 5 [/SUP], Elena Tagliabue[SUP] 14 [/SUP], Janet Chou[SUP] 8 [/SUP], Antonio E Pontiroli[SUP] 15 [/SUP], Federica Meloni[SUP] 16 [/SUP], Andreas Wack[SUP] 4 [/SUP], Nicasio Mancini[SUP] 17 [/SUP], Ivan Zanoni[SUP] 18 [/SUP]
Affiliations
Abstract
Severe coronavirus disease 2019 (COVID-19) is characterized by overproduction of immune mediators, but the role of interferons (IFNs) of the type I (IFN-I) or type III (IFN-III) families remains debated. We scrutinized the production of IFNs along the respiratory tract of COVID-19 patients and found that high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity. Production of specific IFN-III, but not IFN-I, members denotes patients with a mild pathology and efficiently drives the transcription of genes that protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In contrast, compared to subjects with other infectious or noninfectious lung pathologies, IFNs are overrepresented in the lower airways of patients with severe COVID-19 that exhibit gene pathways associated with increased apoptosis and decreased proliferation. Our data demonstrate a dynamic production of IFNs in SARS-CoV-2-infected patients and show IFNs play opposing roles at distinct anatomical sites.
Keywords: COVID-19; SARS-CoV-2; Type I IFN; Type III IFN; airways; dendritic cell; epithelial cell; interferon; lung; pattern recognition receptor.
. 2021 Aug 19;S0092-8674(21)00990-9.
doi: 10.1016/j.cell.2021.08.016. Online ahead of print.
The interferon landscape along the respiratory tract impacts the severity of COVID-19
Benedetta Sposito[SUP] 1 [/SUP], Achille Broggi[SUP] 2 [/SUP], Laura Pandolfi[SUP] 3 [/SUP], Stefania Crotta[SUP] 4 [/SUP], Nicola Clementi[SUP] 5 [/SUP], Roberto Ferrarese[SUP] 6 [/SUP], Sofia Sisti[SUP] 6 [/SUP], Elena Criscuolo[SUP] 6 [/SUP], Roberto Spreafico[SUP] 7 [/SUP], Jaclyn M Long[SUP] 8 [/SUP], Alessandro Ambrosi[SUP] 9 [/SUP], Enju Liu[SUP] 10 [/SUP], Vanessa Frangipane[SUP] 3 [/SUP], Laura Saracino[SUP] 3 [/SUP], Sara Bozzini[SUP] 3 [/SUP], Laura Marongiu[SUP] 11 [/SUP], Fabio A Facchini[SUP] 11 [/SUP], Andrea Bottazzi[SUP] 12 [/SUP], Tommaso Fossali[SUP] 13 [/SUP], Riccardo Colombo[SUP] 13 [/SUP], Massimo Clementi[SUP] 5 [/SUP], Elena Tagliabue[SUP] 14 [/SUP], Janet Chou[SUP] 8 [/SUP], Antonio E Pontiroli[SUP] 15 [/SUP], Federica Meloni[SUP] 16 [/SUP], Andreas Wack[SUP] 4 [/SUP], Nicasio Mancini[SUP] 17 [/SUP], Ivan Zanoni[SUP] 18 [/SUP]
Affiliations
- PMID: 34492226
- DOI: 10.1016/j.cell.2021.08.016
Abstract
Severe coronavirus disease 2019 (COVID-19) is characterized by overproduction of immune mediators, but the role of interferons (IFNs) of the type I (IFN-I) or type III (IFN-III) families remains debated. We scrutinized the production of IFNs along the respiratory tract of COVID-19 patients and found that high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity. Production of specific IFN-III, but not IFN-I, members denotes patients with a mild pathology and efficiently drives the transcription of genes that protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In contrast, compared to subjects with other infectious or noninfectious lung pathologies, IFNs are overrepresented in the lower airways of patients with severe COVID-19 that exhibit gene pathways associated with increased apoptosis and decreased proliferation. Our data demonstrate a dynamic production of IFNs in SARS-CoV-2-infected patients and show IFNs play opposing roles at distinct anatomical sites.
Keywords: COVID-19; SARS-CoV-2; Type I IFN; Type III IFN; airways; dendritic cell; epithelial cell; interferon; lung; pattern recognition receptor.