Maturation signatures of conventional dendritic cell subtypes in COVID‐19 suggest direct viral sensing
| Autor: | Valeria Bevilacqua, Fabio A. Facchini, Roberto Spreafico, Nicasio Mancini, Luca Nespoli, Giulia Protti, Maria Lucia Sarnicola, Valeria Ranzani, Francesca Mingozzi, Andrea Biondi, Serena Curti, Laura Marongiu, Mariella D'Angiò, Mariacristina Crosti, Sergio Abrignani, Francesca Granucci, Laura Rachele Bettini, Anna Rita Putignano, Nicolò Tamini, Lorenzo Salviati, Nicola Clementi, Mihai Valache |
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| Přispěvatelé: | 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, Protti, G, Facchini, F, Valache, M, Mingozzi, F, Ranzani, V, Putignano, A, Salviati, L, Bevilacqua, V, Curti, S, Crosti, M, Sarnicola, M, D'Angio, M, Bettini, L, Biondi, A, Nespoli, L, Tamini, N, Clementi, N, Mancini, N, Abrignani, S, Spreafico, R, Granucci, F |
| Rok vydání: | 2021 |
| Předmět: |
SARS-CoV-2
dendritic cell Effector T-Lymphocytes Immunology Antigen presentation Immunity to infection COVID-19 Interleukin Dendritic Cells Biology Lymphocyte Activation single cell transcriptomics Proinflammatory cytokine Immune system Downregulation and upregulation Humans Immunology and Allergy Research Article|Basic Basic Signal transduction Conventional Dendritic Cell Signal Transduction Research Article |
| Zdroj: | European Journal of Immunology |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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