Impaired function and delayed regeneration of dendritic cells in COVID-19

Winheim, E; Rinke, L; Lutz, K; Reischer, A; Leutbecher, A; Wolfram, L; Rausch, L; Kranich, J; Wratil, PR; Huber, JE; Baumjohann, D; Rothenfusser, S; Schubert, B; Hilgendorff, A; Hellmuth, JC; Scherer, C; Muenchhoff, M; von Bergwelt-Baildon, M; Stark, K; Straub, T; Brocker, T; Keppler, OT; Subklewe, M; Krug, AB (2021) Impaired function and delayed regeneration of dendritic cells in COVID-19. PLoS Pathog, 2021 vol. 17(10) e1009742 https://doi.org/10.1371/journal.ppat.1009742
PMID: 34614036

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.

See LMU press release 27.10.2021: https://www.lmu.de/de/newsroom/newsuebersicht/news/wie-covid-19-das-immunsystem-veraendert.html