title: Gene expression and antiviral activity of alpha/beta interferons and interleukin-29 in virus-infected human myeloid dendritic cells.
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.
authors: Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland.
authors: Pamela
authors: P
authors: Osterlund
authors: Ville
authors: V
authors: Veckman
authors: Jukka
authors: J
authors: Sirén
authors: Kevin M
authors: KM
authors: Klucher
authors: John
authors: J
authors: Hiscott
authors: Sampsa
authors: S
authors: Matikainen
authors: Ilkka
authors: I
authors: Julkunen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis / Q000235:genetics; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D000998:Antiviral Agents / Q000235:genetics / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000494:pharmacology; D016899:Interferon-beta / Q000096:biosynthesis* / Q000494:pharmacology; D007372:Interferons; D007378:Interleukins / Q000096:biosynthesis* / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D029082:Sendai virus / Q000502:physiology*; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051193:Toll-Like Receptors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology; D000095022:Interferon Lambda
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000943:Antigens, Differentiation; D000998:Antiviral Agents; D016207:Cytokines; D004268:DNA-Binding Proteins; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha; D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051193:Toll-Like Receptors; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C494232:IRF3 protein, human; C507779:MYD88 protein, human; C470409:TICAM1 protein, human; C495344:TLR3 protein, human; C495348:TLR7 protein, human; C495349:TLR8 protein, human