Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity.

Autor: Saichi M; Université de Paris, INSERM U976, Paris, France., Ladjemi MZ; Institut Cochin, INSERM U1016, CNRS UMR8104, Université de Paris, Paris, France.; Service de Médecine Intensive & Réanimation, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris. Centre & Université de Paris, Paris, France., Korniotis S; Université de Paris, INSERM U976, Paris, France., Rousseau C; Institut Cochin, INSERM U1016, CNRS UMR8104, Université de Paris, Paris, France., Ait Hamou Z; Institut Cochin, INSERM U1016, CNRS UMR8104, Université de Paris, Paris, France.; Service de Médecine Intensive & Réanimation, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris. Centre & Université de Paris, Paris, France., Massenet-Regad L; Université de Paris, INSERM U976, Paris, France.; Université Paris-Saclay, Saint-Aubin, France., Amblard E; Université de Paris, INSERM U976, Paris, France.; Université de Paris, Centre de Recherches Interdisciplinaires, Paris, France., Noel F; Université de Paris, INSERM U976, Paris, France., Marie Y; Institut du Cerveau (ICM), Plateforme de Génotypage Séquençage, Paris, France.; Sorbonne Universités, Université Pierre et Marie Curie, Paris, France., Bouteiller D; Institut du Cerveau (ICM), Plateforme de Génotypage Séquençage, Paris, France., Medvedovic J; Université de Paris, INSERM U976, Paris, France., Pène F; Institut Cochin, INSERM U1016, CNRS UMR8104, Université de Paris, Paris, France.; Service de Médecine Intensive & Réanimation, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris. Centre & Université de Paris, Paris, France., Soumelis V; Université de Paris, INSERM U976, Paris, France. vassili.soumelis@aphp.fr.; AP-HP, Hôpital Saint-Louis, Laboratoire d'Immunologie-Histocompatibilité, Paris, France. vassili.soumelis@aphp.fr.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2021 May; Vol. 23 (5), pp. 538-551. Date of Electronic Publication: 2021 May 10.
DOI: 10.1038/s41556-021-00681-2
Abstrakt: COVID-19 can lead to life-threatening respiratory failure, with increased inflammatory mediators and viral load. Here, we perform single-cell RNA-sequencing to establish a high-resolution map of blood antigen-presenting cells (APCs) in 15 patients with moderate or severe COVID-19 pneumonia, at day 1 and day 4 post admission to intensive care unit or pulmonology department, as well as in 4 healthy donors. We generated a unique dataset of 81,643 APCs, including monocytes and rare dendritic cell (DC) subsets. We uncovered multi-process defects in antiviral immune defence in specific APCs from patients with severe disease: (1) increased pro-apoptotic pathways in plasmacytoid DCs (pDCs, key effectors of antiviral immunity), (2) a decrease of the innate sensors TLR9 and DHX36 in pDCs and CLEC9a + DCs, respectively, (3) downregulation of antiviral interferon-stimulated genes in monocyte subsets and (4) a decrease of major histocompatibility complex (MHC) class II-related genes and MHC class II transactivator activity in cDC1c + DCs, suggesting viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore the defective immune defence.
Databáze: MEDLINE
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