title: Autocrine type I IFN and contact with endothelium promote the presentation of influenza A virus by monocyte-derived APC.
abstract: Purified monocytes infected with influenza A virus do not become mature dendritic cells (DCs) and they present viral peptides poorly to autologous memory T cells. In this study, we investigated whether influenza A-infected monocytes matured to DCs with a high capacity to stimulate T cells when they were infected with influenza A virus in a model tissue setting wherein they were cocultured with endothelium grown on a type I collagen matrix. Intercellular interactions with endothelium strongly promoted the Ag-presenting capacity of monocyte-derived cells infected with influenza A virus, and the heterologous coculture system also enhanced production of IFN-alpha by monocytes in the absence of plasmacytoid cells. Production of IFN-alpha in the presence of endothelium correlated with monocyte differentiation to mature DCs and their ability to stimulate proliferation and IFN-gamma production by autologous T cells. Monocyte-derived cells that developed into migratory DCs promoted proliferation of influenza A virus-specific CD4(+) and CD8(+) cells, whereas those that developed into macrophages promoted proliferation of CD8(+) T cells only. This onset of APC activity could be partially blocked with Ab to the IFN-alphabeta receptor when monocytes were infected with UV-treated virus, but neutralizing this pathway was inconsequential when monocytes were infected with live virus. Thus, type I IFN and direct contact with endothelium promote development of influenza A virus-presenting activity in monocyte-derived cells in a setting in which this differentiation does not depend on plasmacytoid cells. However, when infected with live influenza virus, the role of type I IFN in mediating differentiation and Ag-presenting capacity is expendable, apparently due to other mechanisms of virus-mediated activation.
authors.affiliation: Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mt. Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Qu
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Moran
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
mesh_terms: D000328:Adult; D017951:Antigen Presentation / Q000276:immunology / Q000502:physiology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019898:Autocrine Communication / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology* / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000821:virology; D005312:Fetal Blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007370:Interferon Type I / Q000096:biosynthesis / Q000502:physiology*; D016898:Interferon-alpha / Q000096:biosynthesis / Q000502:physiology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology
chemical_list: D007370:Interferon Type I; D016898:Interferon-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor