Gene expression and antiviral activity of alpha/beta interferons and interleukin-29 in virus-infected human myeloid dendritic cells.
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.
Osterlund
Pamela
P
Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland.
Veckman
Ville
V
Sirén
Jukka
J
Klucher
Kevin M
KM
Hiscott
John
J
Matikainen
Sampsa
S
Julkunen
Ilkka
I
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
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