title: Novel mechanism of immunosuppression by influenza virus haemagglutinin: selective suppression of interleukin 12 p35 transcription in murine bone marrow-derived dendritic cells.
abstract: Infection with influenza virus strongly predisposes an individual to bacterial superinfection, which is often the significant cause of morbidity and mortality during influenza epidemics. Little is known about the immunomodulating properties of the virus that lead to this phenomenon, but the effect of the viral components on the development of immune dendritic cells (DCs) may prove vital. In this study, activation of and cytokine secretion by bacterial lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) following treatment with the influenza virus major antigen haemagglutinin (HA) were examined. HA selectively inhibits the release of LPS-induced interleukin 12 (IL12) p70, which is independent of IL10 secretion. Suppression occurs at the transcriptional level, with selective inhibition of p35- and not p40-subunit mRNA expression. The downregulation of IL12 p70 by influenza HA is a novel and unexplored pathway that may be relevant in the predisposition to bacterial superinfection associated with influenza virus infections.
authors.affiliation: Immunovirology Laboratory, Institute of Immunology and Biology Department, National University of Ireland, Maynooth, Co. Kildare, Ireland.
authors.forename: Cariosa M
authors.initials: CM
authors.lastname: Noone
authors.affiliation: Immunovirology Laboratory, Institute of Immunology and Biology Department, National University of Ireland, Maynooth, Co. Kildare, Ireland.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Lewis
authors.affiliation: Immunovirology Laboratory, Institute of Immunology and Biology Department, National University of Ireland, Maynooth, Co. Kildare, Ireland.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Frawely
authors.affiliation: National Institute for Biological Standards and Controls, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3QG, UK.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Newman
authors.affiliation: Mucosal Immunology Laboratory, Institute of Immunology, National University of Ireland, Maynooth, Co. Kildare, Ireland.
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Mahon
authors.affiliation: Immune Regulation Research Group, Biochemistry Department, Trinity College Dublin, Ireland.
authors.forename: Kingston H
authors.initials: KH
authors.lastname: Mills
authors.affiliation: Immunovirology Laboratory, Institute of Immunology and Biology Department, National University of Ireland, Maynooth, Co. Kildare, Ireland.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015536:Down-Regulation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D009980:Influenza A virus / Q000378:metabolism / Q000472:pathogenicity*; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism*; D053765:Interleukin-12 Subunit p35; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; C508858:IL12A protein, human; D053765:Interleukin-12 Subunit p35; D008070:Lipopolysaccharides; D021122:Protein Subunits; D012333:RNA, Messenger; D018664:Interleukin-12