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Winheim, Elena ORCID logoORCID: https://orcid.org/0000-0002-0364-662X; Rinke, Linus ORCID logoORCID: https://orcid.org/0000-0002-7563-7116; Lutz, Konstantin ORCID logoORCID: https://orcid.org/0000-0002-6263-467X; Reischer, Anna; Leutbecher, Alexandra; Wolfram, Lina; Rausch, Lisa; Kranich, Jan ORCID logoORCID: https://orcid.org/0000-0002-9928-4132; Wratil, Paul R.; Huber, Johanna E.; Baumjohann, Dirk ORCID logoORCID: https://orcid.org/0000-0001-8385-8288; Rothenfusser, Simon ORCID logoORCID: https://orcid.org/0000-0003-1151-7614; Schubert, Benjamin; Hilgendorff, Anne; Hellmuth, Johannes C.; Scherer, Clemens ORCID logoORCID: https://orcid.org/0000-0003-2816-6793; Münchhoff, Maximilian ORCID logoORCID: https://orcid.org/0000-0001-7016-0470; Bergwelt-Baildon, Michael von; Stark, Konstantin; Straub, Tobias ORCID logoORCID: https://orcid.org/0000-0002-0547-0453; Brocker, Thomas; Keppler, Oliver T. ORCID logoORCID: https://orcid.org/0000-0002-1384-8946; Subklewe, Marion and Krug, Anne B. ORCID logoORCID: https://orcid.org/0000-0002-9556-7207 (2021): Impaired function and delayed regeneration of dendritic cells in COVID-19.
In: PLOS Pathogens 17(10), e1009742 [PDF, 5MB]


Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DCs) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute illness to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage−HLADR+ cells lacking DC markers. Increased frequency of CD163+ CD14+ cells within the recently discovered DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of programmed death-ligand 1 (PD-L1) in conventional DCs (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naïve CD4+ T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.

Author summary: Dendritic cells (DCs) recognize viral infections and trigger innate and adaptive antiviral immunity. COVID-19 severity is greatly influenced by the host immune response and modulation of DC generation and function after SARS-CoV-2 infection could play an important role in this disease. This study identifies a long-lasting reduction of DCs in the blood of COVID-19 patients and a functional impairment of these cells. Downregulation of costimulatory molecule CD86 and upregulation of inhibitory molecule PD-L1 in conventional DCs correlated with disease severity and were accompanied by a reduced ability to stimulate T cells. A higher frequency of CD163+ CD14+ cells in the DC3 subpopulation correlated with systemic inflammation suggesting that these cells may play a role in inflammatory responses of COVID-19 patients. Depletion and functional impairment of DCs beyond the acute phase of the disease may have consequences for susceptibility to secondary infections and clinical management of COVID-19 patients.

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