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Maturation signatures of conventional dendritic cell subtypes in COVID‐19 suggest direct viral sensing

  • Marongiu, Laura1, 2
  • Protti, Giulia1, 2
  • Facchini, Fabio A.1
  • Valache, Mihai1
  • Mingozzi, Francesca1
  • Ranzani, Valeria2
  • Putignano, Anna Rita2
  • Salviati, Lorenzo1, 2
  • Bevilacqua, Valeria2
  • Curti, Serena2
  • Crosti, Mariacristina2
  • Sarnicola, Maria Lucia2
  • D'Angiò, Mariella3
  • Bettini, Laura Rachele3
  • Biondi, Andrea3
  • Nespoli, Luca1
  • Tamini, Nicolò1
  • Clementi, Nicola4, 5
  • Mancini, Nicasio4, 5
  • Abrignani, Sergio2, 6
  • And 2 more
  • 1 University of Milano‐Bicocca, Italy , (Italy)
  • 2 National Institute of Molecular Genetics “Romeo ed Enrica Invernizzi”, Italy , (Italy)
  • 3 MetabERN‐University of Milano‐Bicocca‐Fondazione MBBM‐Ospedale, Italy , (Italy)
  • 4 Vita‐Salute San Raffaele University, Italy , (Italy)
  • 5 IRCCS San Raffaele Hospital, Italy , (Italy)
  • 6 University of Milano, Italy , (Italy)
  • 7 University of California
Published Article
European Journal of Immunology
Wiley (John Wiley & Sons)
Publication Date
Aug 01, 2021
DOI: 10.1002/eji.202149298
PMID: 34333764
PMCID: PMC8420462
PubMed Central
  • Immunity to infection
  • Research Article
  • Basic
External links


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 interferon‐stimulated genes and interleukin (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. This article is protected by copyright. All rights reserved

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