Open AccessImpaired function and delayed regeneration of dendritic cells in COVID-19
Author(s) -
Elena Winheim,
Linus Rinke,
Konstantin Lutz,
Anna Reischer,
Alexandra Leutbecher,
Lina Wolfram,
Lisa Rausch,
Jan Kranich,
Paul R. Wratil,
Johanna E. Huber,
Dirk Baumjohann,
Simon Rothenfußer,
Benjamin Schubert,
Anne Hilgendorff,
Johannes C. Hellmuth,
Clemens Scherer,
Maximilian Muenchhoff,
Michael von BergweltBaildon,
Konstantin Stark,
Tobias Straub,
Thomas Brocker,
Oliver T. Keppler,
Marion Subklewe,
Anne B. Krug
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009742
Subject(s) - immunology , cd14 , immune system , downregulation and upregulation , cd86 , inflammation , acquired immune system , monocyte , cd163 , dendritic cell , plasmacytoid dendritic cell , biology , medicine , t cell , macrophage , gene , in vitro , biochemistry
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.