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Maturation signatures of conventional dendritic cell subtypes in COVID-19 suggest direct viral sensing.
Marongiu, Laura; Protti, Giulia; Facchini, Fabio A; Valache, Mihai; Mingozzi, Francesca; Ranzani, Valeria; Putignano, Anna Rita; Salviati, Lorenzo; Bevilacqua, Valeria; Curti, Serena; Crosti, Mariacristina; Sarnicola, Maria Lucia; D'Angiò, Mariella; Bettini, Laura Rachele; Biondi, Andrea; Nespoli, Luca; Tamini, Nicolò; Clementi, Nicola; Mancini, Nicasio; Abrignani, Sergio; Spreafico, Roberto; Granucci, Francesca.
  • Marongiu L; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
  • Protti G; National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.
  • Facchini FA; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
  • Valache M; National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.
  • Mingozzi F; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
  • Ranzani V; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
  • Putignano AR; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
  • Salviati L; National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.
  • Bevilacqua V; National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.
  • Curti S; Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
  • Crosti M; National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.
  • Sarnicola ML; National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.
  • D'Angiò M; National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.
  • Bettini LR; National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.
  • Biondi A; National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi", Milan, Italy.
  • Nespoli L; Pediatric Department and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale, San Gerardo, Monza, Italy.
  • Tamini N; Pediatric Department and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale, San Gerardo, Monza, Italy.
  • Clementi N; Pediatric Department and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale, San Gerardo, Monza, Italy.
  • Mancini N; ASST san Gerardo Hospital, School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
  • Abrignani S; ASST san Gerardo Hospital, School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
  • Spreafico R; Laboratory of Medical Microbiology and Virology, Vita-Salute San Raffaele University, Milan, Italy.
  • Granucci F; IRCCS San Raffaele Hospital, Milan, Italy.
Eur J Immunol ; 52(1): 109-122, 2022 01.
Article in English | MEDLINE | ID: covidwho-1332967
ABSTRACT
Growing evidence suggests that conventional dendritic cells (cDCs) undergo aberrant maturation in COVID-19, which negatively affects T-cell activation. The presence of effector T cells in patients with mild disease and dysfunctional T cells in severely ill patients suggests that adequate T-cell responses limit disease severity. Understanding how cDCs cope with SARS-CoV-2 can help elucidate how protective immune responses are generated. Here, we report that cDC2 subtypes exhibit similar infection-induced gene signatures, with the upregulation of IFN-stimulated genes and IL-6 signaling pathways. Furthermore, comparison of cDCs between patients with severe and mild disease showed severely ill patients to exhibit profound downregulation of genes encoding molecules involved in antigen presentation, such as MHCII, TAP, and costimulatory proteins, whereas we observed the opposite for proinflammatory molecules, such as complement and coagulation factors. Thus, as disease severity increases, cDC2s exhibit enhanced inflammatory properties and lose antigen presentation capacity. Moreover, DC3s showed upregulation of anti-apoptotic genes and accumulated during infection. Direct exposure of cDC2s to the virus in vitro recapitulated the activation profile observed in vivo. Our findings suggest that SARS-CoV-2 interacts directly with cDC2s and implements an efficient immune escape mechanism that correlates with disease severity by downregulating crucial molecules required for T-cell activation.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Dendritic Cells / Lymphocyte Activation / T-Lymphocytes / Signal Transduction / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Eur J Immunol Year: 2022 Document Type: Article Affiliation country: Eji.202149298

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Dendritic Cells / Lymphocyte Activation / T-Lymphocytes / Signal Transduction / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Eur J Immunol Year: 2022 Document Type: Article Affiliation country: Eji.202149298