Human type 2 myeloid dendritic cells produce interferon-? and amplify interferon-? in response to hepatitis C virus infection.

ABSTRACT: BACKGROUND & AIMS:The type III interferons (IFN-?s: interleukin [IL]-28a, IL-28b, and IL-29) have important roles in hepatitis C virus (HCV) infection, but little is understood about what cells produce these cytokines or how production is activated. We investigated whether human immune cells recognize HCV-infected cells and respond by producing IFN-?. METHODS:We cultured healthy human peripheral blood mononuclear cells (PBMCs) with different populations of immune cells and Japanese fulminant hepatitis-1 (JFH-1) HCV-infected Huh7.5 (cell culture-derived HCV particles [HCVcc]/Huh7.5) cells. RESULTS:Human PBMCs recognized HCVcc/Huh7.5 cells and responded by producing IFN-?, IFN-?, and IFN-?. A rare subset of myeloid dendritic cells (mDCs), which are blood DC antigen (BDCA)+ (also called mDC2 cells), were the major source of IL-28 and IL-29 production in response to HCVcc/Huh7.5 cells. Plasmacytoid DCs produced IFN-?, whereas natural killer and natural killer T cells were the main source of IFN-? production in co-culture experiments. Of the endosomal Toll-like receptors (TLRs)3, 7, 8, and 9, only TLR3 or double-stranded HCV RNA induced production of IL-28 and IL-29 by mDC2s; endosomal maturation was required. Production of IFN-? and IFN-? were linked-IFN-? increased production of IFN-? by plasmacytoid DCs and IFN-? significantly increased production of IFN-?. CONCLUSIONS:mDC2s are a major source of IFN-? production by PBMCs in response to HCVcc/Huh7.5 cells. mDC2s are activated through the TLR3 pathway, indicating that human DCs efficiently can initiate an immune response against HCV infection. IFN-? therefore has an important role in HCV infection.

SUBMITTER: Zhang S 

PROVIDER: S-EPMC3568254 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature