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10.1371/journal.ppat.1009878

http://scihub22266oqcxt.onion/10.1371/journal.ppat.1009878
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suck abstract from ncbi


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pmid34473805      PLoS+Pathog 2021 ; 17 (9): e1009878
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  • Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection #MMPMID34473805
  • Severa M; Diotti RA; Etna MP; Rizzo F; Fiore S; Ricci D; Iannetta M; Sinigaglia A; Lodi A; Mancini N; Criscuolo E; Clementi M; Andreoni M; Balducci S; Barzon L; Stefanelli P; Clementi N; Coccia EM
  • PLoS Pathog 2021[Sep]; 17 (9): e1009878 PMID34473805show ga
  • 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.
  • |Adult[MESH]
  • |Aged, 80 and over[MESH]
  • |Asymptomatic Infections[MESH]
  • |COVID-19/*immunology[MESH]
  • |Cell Line, Tumor[MESH]
  • |Dendritic Cells/*classification/immunology/virology[MESH]
  • |Epithelial Cells/cytology[MESH]
  • |Female[MESH]
  • |Hospitalization[MESH]
  • |Humans[MESH]
  • |Interferon Type I/immunology/*metabolism[MESH]
  • |Lung/cytology[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Neuropilin-1/metabolism[MESH]
  • |Phenotype[MESH]
  • |SARS-CoV-2/*immunology[MESH]
  • |Severity of Illness Index[MESH]


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