The antiviral immune response in human conventional dendritic cells is controlled by the mammalian target of rapamycin. Issue 4 (7th July 2014)

• Record Type: Journal Article
• Authors: Fekete, Tünde; Pazmandi, Kitti; Szabo, Attila; Bacsi, Attila; Koncz, Gabor; Rajnavölgyi, Eva
• Is Part Of: Journal of leukocyte biology. Volume 96:Issue 4(2014)
• Page Start: 579
• Page End: 589
• Publication Date: 2014-07-07
• Subjects: interferon -- Toll-like receptor 3 -- signal transduction -- viral; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.2A0114-048RR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Induction of type I and III IFNs depends on mTOR, and acts in collaboration with TBK1 in human conventional DCs. 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.