RLR-mediated production of interferon-β by a human dendritic cell subset and its role in virus-specific immunity

Cytosolic RIG-I-like helicases (RLR) are PRRs involved in type IIFN production and antiviral immunity. This study focuses to the comparison of the expression, function, and signaling cascades associated to RLR in the previously identified CD14^-DC-SIGN⁺PPARγ^lowCD1a⁺ and CD14^lowDC-SIGN⁺PPARγ^highCD1a human moDC subsets. Our results revealed that the expression of RLR genes and proteins as well as the activity of the coupled signaling pathways are significantly higher in the CD1a⁺ subset than in its phenotyp-ically and functionally distinct counterpart. Specific activation of RLR in moDCs by poly(I:C) or influenza virus was shown to induce the secretion of IFN-β via IRF3, whereas induction of proinflammatory cytokine responses were predominantly controlled by TLR3. The requirement of RLR-mediated signaling in CD1a⁺ moDCs for priming naïve CD8⁺ T lymphocytes and inducing influenza virus-specific cellular immune responses was confirmed by RIG-I/MDA5 silencing, which abrogated these functions. Our results demonstrate the subset-specific activation of RLR and the underlying mechanisms behind its cytokine secretion profile and identify CD1a⁺ moDCs as an inflammatory subset with specialized functional activities. We also provide evidence that this migratory DC subset can be detected in human tonsil and reactive LNs.