title: The antiviral immune response in human conventional dendritic cells is controlled by the mammalian target of rapamycin.
abstract: Type I and III IFNs are crucial, soluble components of potent antiviral responses. It has been explored recently that mTOR is involved in the regulation of IFN-α/β production by pDCs, albeit its role in the induction of IFN responses in cDCs remained unrevealed. In this study, we demonstrate that the PI3K/mTOR pathway is indispensable for eliciting intact type I and III IFN responses in moDCs stimulated with polyI:C. The inhibition of mTOR functionality by rapamycin impairs the pIRF3 and also a few members of the MAPK family, suggesting that mTOR contributes to the activation of multiple signaling pathways in the presence of viral antigens. Furthermore, rapamycin-treated moDCs show decreased capacity to prime IFN-γ secretion by naive CD8(+) T-lymphocytes. As in moDCs, mTOR-mediated regulation is also essential for the production of type I and III IFNs in circulating CD1c(+) DCs. To our best knowledge, these results demonstrate for the first time that mTOR has an impact on the functional activities of cDCs via modulating the outcome of IFN secretion.
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Tünde
authors.initials: T
authors.lastname: Fekete
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Kitti
authors.initials: K
authors.lastname: Pazmandi
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Szabo
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Bacsi
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Koncz
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary evaraj@med.unideb.hu.
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavölgyi
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D018949:Antigens, CD1; D000954:Antigens, Surface; D006023:Glycoproteins; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D019869:Phosphatidylinositol 3-Kinases; D011070:Poly I-C; D017346:Protein Serine-Threonine Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C437944:CD1C protein, human; C494232:IRF3 protein, human; C403191:TBK1 protein, human
keywords: Toll-like receptor 3; interferon; signal transduction; viral