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.

journal_name

J Leukoc Biol

authors

Szabo A,Bene K,Gogolák P,Réthi B,Lányi Á,Jankovich I,Dezső B,Rajnavölgyi E

doi

10.1189/jlb.0711360

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

159-69

issue

1

eissn

0741-5400

issn

1938-3673

pii

jlb.0711360

journal_volume

92

pub_type

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