Open AccessExpression of Type III Interferon (IFN) in the Vaginal Mucosa Is Mediated Primarily by Dendritic Cells and Displays Stronger Dependence on NF-κB than Type I IFNs
Author(s) -
Marie B. Iversen,
Nina Ank,
Jesper Melchjorsen,
Søren R. Paludan
Publication year - 2010
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02591-09
Subject(s) - biology , interferon , interferon type i , tlr9 , interferon regulatory factors , herpes simplex virus , receptor , signal transduction , pattern recognition receptor , innate immune system , immune system , microbiology and biotechnology , cd11c , immunology , gene expression , virus , gene , genetics , phenotype , dna methylation
Interferons (IFNs) are induced as an initial response to viral infection after recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). Here, we report that different PAMPs induce type I and III IFN expression at different ratios after mucosal administration in the vaginas of mice and that Toll-like receptor 9 (TLR9) stimulation evokes a particularly strong IFN-lambda response, which is essential for optimal antiviral protection. Depletion of CD11c(+) cells in vivo revealed that dendritic cells (DCs) in the vaginal epithelium are a key source of type I and III IFNs during herpes simplex virus infection and after specific stimulation of TLR9. A comparison of the signaling pathways activated by TLR9 and cytoplasmic PRRs, which induced lower levels of IFN-lambda, revealed that high-level induction of IFN-lambda correlated with strong activation of NF-kappaB p65. Inhibition of the NF-kappaB and interferon regulatory factor 3 (IRF-3) pathways with the NEMO-binding domain peptide and small interfering RNA (siRNA), respectively, revealed that transcription of the type III IFN genes was more dependent on the NF-kappaB pathway than that of the type I IFN genes, which relied more on the IRF system. Thus, the type I and III IFN genes are not induced through entirely identical pathways, which indicates differential expression of these two types of IFNs under certain conditions.