Type I Interferons (IFN-I) are a family of potent antiviral cytokines that act through the direct restriction of viral replication and by enhancing antiviral immunity. However, these powerful cytokines are a caged lion, as excessive and sustained IFN-I production can drive immunopathology during infection, and aberrant IFN-I production is a feature of several types of autoimmunity. As specialized producers of IFN-I plasmacytoid (p), dendritic cells (DCs) can secrete superb quantities and a wide breadth of IFN-I isoforms immediately after infection or stimulation, and are the focus of this review. Notably, a few days after viral infection pDCs tune down their capacity for IFN-I production, producing less cytokines in response to both the ongoing infection and unrelated secondary stimulations. This process, hereby referred to as “pDC exhaustion”, favors viral persistence and associates with reduced innate responses and increased susceptibility to secondary opportunistic infections. On the other hand, pDC exhaustion may be a compromise to avoid IFN-I driven immunopathology. In this review we reflect on the mechanisms that initially induce IFN-I and subsequently silence their production by pDCs during a viral infection. While these processes have been long studied across numerous viral infection models, the 2019 coronavirus disease (COVID-19) pandemic has brought their discussion back to the fore, and so we also discuss emerging results related to pDC-IFN-I production in the context of COVID-19.
【저자키워드】 COVID-19, SARS-CoV-2, viral infection, Influenza, HCV, HBV, HIV-1, IFN-I, plasmacytoid dendritic cells, LCMV, 【초록키워드】 coronavirus disease, Autoimmunity, viral infection, coronavirus, pandemic, Cytokines, susceptibility, Infection, interferons, cytokine, immunopathology, dendritic cells, pDCs, family, Viral, viral replication, 2019 coronavirus disease, IFN-I, type I interferons, viral persistence, antiviral immunity, mechanism, dendritic cell, breadth, Stimulation, opportunistic Infections, referred to, focus, innate response, favor, antiviral cytokines, compromise, while, isoform, DCs, reduced, less, induce, producing, Type, sustained, antiviral cytokine, pDC, secrete, 【제목키워드】 Exhaustion, induction, finding, Type,