2 research outputs found
How dendritic cells sense and respond to viral infections.
Abstract
The ability of dendritic cells (DCs) to sense viral pathogens and orchestrate a proper immune response makes them one of the key players in antiviral immunity. Different DC subsets have complementing functions during viral infections, some specialize in antigen presentation and cross-presentation and others in the production of cytokines with antiviral activity, such as type I interferons. In this review, we summarize the latest updates concerning the role of DCs in viral infections, with particular focus on the complex interplay between DC subsets and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Despite being initiated by a vast array of immune receptors, DC-mediated antiviral responses often converge towards the same endpoint, that is the production of proinflammatory cytokines and the activation of an adaptive immune response. Nonetheless, the inherent migratory properties of DCs make them a double-edged sword and often viral recognition by DCs results in further viral dissemination. Here we illustrate these various aspects of the antiviral functions of DCs and also provide a brief overview of novel antiviral vaccination strategies based on DCs targeting
Maturation signatures of conventional dendritic cell subtypes in COVID‐19 suggest direct viral sensing
Growing evidence suggests that conventional dendritic cells (cDCs) undergo
aberrant maturation in COVID-19, which negatively affects T-cell activation. The presence of
effector T cells in patients with mild disease and dysfunctional T cells in severely ill patients
suggests that adequate T-cell responses limit disease severity. Understanding how cDCs cope
with SARS-CoV-2 can help elucidate how protective immune responses are generated. Here, we
report that cDC2 subtypes exhibit similar infection-induced gene signatures, with the
upregulation of interferon-stimulated genes and interleukin (IL)-6 signaling pathways.
Furthermore, comparison of cDCs between patients with severe and mild disease showed
severely ill patients to exhibit profound downregulation of genes encoding molecules involved
in antigen presentation, such as MHCII, TAP, and costimulatory proteins, whereas we observed
the opposite for proinflammatory molecules, such as complement and coagulation factors. Thus,
as disease severity increases, cDC2s exhibit enhanced inflammatory properties and lose antigen
presentation capacity. Moreover, DC3s showed upregulation of anti-apoptotic genes and
accumulated during infection. Direct exposure of cDC2s to the virus in vitro recapitulated the
activation profile observed in vivo. Our findings suggest that SARS-CoV-2 interacts directly with cDC2s and implements an efficient immune escape mechanism that correlates with disease severity by downregulating crucial molecules required for T-cell activation