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.
【초록키워드】 COVID-19, Monocytes, viral infection, therapy, innate immune response, adaptive, Inflammatory responses, antibody, T cells, SARS-COV-2 infection, susceptibility, disease severity, COVID-19 severity, immunopathology, CD4, viral infections, dendritic cells, monocyte, PD-L1, T cell, Viral, Secondary infection, Host immune response, cells, immune responses, Patient, Clinical management, Mild, systemic inflammation, expansion, persistent, Adaptive immune response, antiviral immunity, disease, secondary infections, dendritic cell, COVID-19 patients, Blood, hospitalized COVID-19 patient, Inflammatory response, Frequency, regeneration, severe disease, adaptive immune responses, COVID-19 patient, Trigger, manifestation, helper cells, reduction, modulation, acute phase, These cells, alteration, naïve, T follicular helper cells, upregulation, Depletion, healthy controls, CD14, downregulation, antibody-secreting cells, circulating, classical monocytes, CD163, impairment, acute illness, subpopulation, inhibitory, HLADR, monocyte subsets, CD14+ cells, CD86, dysregulated innate immune response, DCs, Cell, consequence, analyzed, identify, the disease, reduced, functional, activated, contribute, recognize, long-lasting, correlated, dysregulated, subset, stimulate, Increased, these cell, accompanied, CD14+ cell, classical monocyte, follicular, 【제목키워드】 COVID-19, dendritic cell, Impaired,