Abstract
Dendritic cells (DCs) respond to microbial infections by undergoing phenotypic maturation and by producing multiple cytokines. In the present study, we analyzed the ability of influenza A and Sendai viruses to induce DC maturation and activate tumor necrosis factor alpha (TNF-alpha), alpha/beta interferon (IFN-alpha/beta), and IFN-like interleukin-28A/B (IFN-lambda2/3) and IL-29 (IFN-lambda1) gene expression in human monocyte-derived myeloid DCs (mDC). The ability of influenza A virus to induce mDC maturation or enhance the expression of TNF-alpha, IFN-alpha/beta, interleukin-28 (IL-28), and IL-29 genes was limited, whereas Sendai virus efficiently induced mDC maturation and enhanced cytokine gene expression. Influenza A virus-induced expression of TNF-alpha, IFN-alpha, IFN-beta, IL-28, and IL-29 genes was, however, dramatically enhanced when cells were pretreated with IFN-alpha. IFN-alpha priming led to increased expression of Toll-like receptor 3 (TLR3), TLR7, TLR8, MyD88, TRIF, and IFN regulatory factor 7 (IRF7) genes and enhanced influenza-induced phosphorylation and DNA binding of IRF3. Influenza A virus also enhanced the binding of NF-kappaB to the respective NF-kappaB elements of the promoters of IFN-beta and IL-29 genes. In mDC IL-29 induced MxA protein expression and possessed antiviral activity against influenza A virus, although this activity was lower than that of IFN-alpha or IFN-beta. Our results show that in human mDCs viruses can readily induce the expression of IL-28 and IL-29 genes whose gene products are likely to contribute to the host antiviral response.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing
-
Adaptor Proteins, Vesicular Transport / biosynthesis
-
Adaptor Proteins, Vesicular Transport / genetics
-
Antigens, Differentiation / biosynthesis
-
Antigens, Differentiation / genetics
-
Antiviral Agents / genetics
-
Antiviral Agents / pharmacology
-
Cell Differentiation
-
Cells, Cultured
-
Cytokines
-
DNA-Binding Proteins / biosynthesis
-
DNA-Binding Proteins / genetics
-
Dendritic Cells / cytology
-
Dendritic Cells / metabolism
-
Dendritic Cells / virology
-
Gene Expression / drug effects
-
Humans
-
Influenza A virus / physiology*
-
Interferon Regulatory Factor-3
-
Interferon-alpha / biosynthesis*
-
Interferon-alpha / pharmacology
-
Interferon-beta / biosynthesis*
-
Interferon-beta / pharmacology
-
Interferons
-
Interleukins / biosynthesis*
-
Interleukins / pharmacology
-
Membrane Glycoproteins / biosynthesis
-
Membrane Glycoproteins / genetics
-
Myeloid Differentiation Factor 88
-
NF-kappa B / metabolism
-
Promoter Regions, Genetic
-
RNA, Messenger / analysis
-
Receptors, Cell Surface / biosynthesis
-
Receptors, Cell Surface / genetics
-
Receptors, Immunologic / biosynthesis
-
Receptors, Immunologic / genetics
-
Sendai virus / physiology*
-
Toll-Like Receptor 3
-
Toll-Like Receptor 7
-
Toll-Like Receptor 8
-
Toll-Like Receptors
-
Transcription Factors / biosynthesis
-
Transcription Factors / genetics
-
Tumor Necrosis Factor-alpha / biosynthesis
-
Tumor Necrosis Factor-alpha / pharmacology
Substances
-
Adaptor Proteins, Signal Transducing
-
Adaptor Proteins, Vesicular Transport
-
Antigens, Differentiation
-
Antiviral Agents
-
Cytokines
-
DNA-Binding Proteins
-
interferon-lambda, human
-
IRF3 protein, human
-
Interferon Regulatory Factor-3
-
Interferon-alpha
-
Interleukins
-
MYD88 protein, human
-
Membrane Glycoproteins
-
Myeloid Differentiation Factor 88
-
NF-kappa B
-
RNA, Messenger
-
Receptors, Cell Surface
-
Receptors, Immunologic
-
TICAM1 protein, human
-
TLR3 protein, human
-
TLR7 protein, human
-
TLR8 protein, human
-
Toll-Like Receptor 3
-
Toll-Like Receptor 7
-
Toll-Like Receptor 8
-
Toll-Like Receptors
-
Transcription Factors
-
Tumor Necrosis Factor-alpha
-
Interferon-beta
-
Interferons