title: RLR-mediated production of interferon-β by a human dendritic cell subset and its role in virus-specific immunity.
abstract: Cytosolic RIG-I-like helicases (RLR) are PRRs involved in type I IFN 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(low)CD1a(+) and CD14(low)DC-SIGN(+)PPARγ(high)CD1a(-) 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 phenotypically 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.
authors.affiliation: Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Szabo
authors.forename: Krisztián
authors.initials: K
authors.lastname: Bene
authors.forename: Péter
authors.initials: P
authors.lastname: Gogolák
authors.forename: Bence
authors.initials: B
authors.lastname: Réthi
authors.forename: Árpád
authors.initials: Á
authors.lastname: Lányi
authors.forename: István
authors.initials: I
authors.lastname: Jankovich
authors.forename: Balázs
authors.initials: B
authors.lastname: Dezső
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavölgyi
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate; D007124:Immunoenzyme Techniques; D007251:Influenza, Human / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D009975:Orthomyxoviridae / Q000276:immunology*; D014066:Palatine Tonsil / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; D016207:Cytokines; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D012333:RNA, Messenger; D016899:Interferon-beta; D053487:DEAD-box RNA Helicases