Influenza A virus-induced IFN-alpha/beta and IL-18 synergistically enhance IFN-gamma gene expression in human T cells.
T cells contribute significantly the to host's early defense against viral and bacterial infections and are essential for clearance of the pathogen. IFN-gamma, a product of activated T and NK cells, has, in addition to its direct antimicrobial activity, a major role in activating cell-mediated immunity. Here we report that cytokines secreted by influenza A virus-infected macrophages are able to induce IFN-gamma synthesis in human T cells. Influenza A virus-infected human peripheral macrophages secreted IFN-alpha/beta, TNF-alpha, IL-1beta, and a recently identified cytokine, IL-18 (or IFN-gamma-inducing factor), whereas the production of IL-12 was not detected. Supernatants collected from virus-infected macrophages induced rapid IFN-gamma mRNA expression and protein production in T cells. This was down-regulated by the addition of neutralizing anti-IFN-alpha/beta Abs, whereas neutralizing anti-IL-12 Abs had no effect on IFN-gamma gene expression. Exogenously added IFN-alpha/beta also rapidly stimulated the synthesis of IFN-gamma mRNA in T cells independently of protein synthesis. IL-18 synergized with IFN-alpha to up-regulate IFN-gamma gene expression and protein production. The data suggest that IFN-alpha/beta and IL-18 produced by macrophages during virus infection may act together to induce IFN-gamma synthesis and, consequently, may play an important role for both of these cytokines in the development of Th1-type immune responses.
Sareneva
T
T
Department of Virology, National Public Health Institute, Helsinki, Finland. timo.sareneva@ktl.fi
Matikainen
S
S
Kurimoto
M
M
Julkunen
I
I
D016207:Cytokines / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006801:Humans; D009980:Influenza A virus; D007251:Influenza, Human / Q000276:immunology; D016898:Interferon-alpha / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D020382:Interleukin-18; D008264:Macrophages / Q000276:immunology / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000821:virology
D016207:Cytokines; D016898:Interferon-alpha; D020382:Interleukin-18; D012333:RNA, Messenger; D016899:Interferon-beta; D007371:Interferon-gamma