Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection

SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, respon...

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Vydáno v:	PLoS pathogens Ročník 17; číslo 9; s. e1009878
Hlavní autoři:	Severa, Martina, Diotti, Roberta A., Etna, Marilena P., Rizzo, Fabiana, Fiore, Stefano, Ricci, Daniela, Iannetta, Marco, Sinigaglia, Alessandro, Lodi, Alessandra, Mancini, Nicasio, Criscuolo, Elena, Clementi, Massimo, Andreoni, Massimo, Balducci, Stefano, Barzon, Luisa, Stefanelli, Paola, Clementi, Nicola, Coccia, Eliana M.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	San Francisco Public Library of Science 02.09.2021 Public Library of Science (PLoS)
Témata:	Antiviral agents Antiviral drugs Asymptomatic Biology and life sciences Carrier state (Communicable diseases) Cell culture Cell interaction Cell surface Chemokines Coronaviruses COVID-19 Cytokine storm Cytokines Dendritic cells Development and progression Disease Epithelial cells Epithelium Experiments Gene expression Health aspects Immune response Immune system Infections Inflammation Interferon Ligands Medicine and health sciences Movement disorders Neuropilin PD-L1 protein Peripheral blood mononuclear cells Phenotypes Pneumonia Replication Respiratory diseases Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 TLR7 protein Toll-like receptors Very Low Frequencies Viral diseases Viral infections Viruses Italy
ISSN:	1553-7374, 1553-7366, 1553-7374
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Shrnutí:	SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro , asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo . These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors are joint senior authors on this work. The authors have declared that no competing interests exist.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1009878