KC from HCV-positive origin showed an elevated IL-29 response, compared to the control panel. In contrast IFN response in HSC did not significantly differ between the HCV-infected and the control group. The source of cells, i.e. non-cirrhotic or cirrhotic tissue, had no measurable see more impact upon any of the

results obtained in this study. Conclusions: Primary human NPC responded to TLR 1 -9 stimulation primarily with induction of inflammatory cytokines in a cell-type specific manner. TLR3 activation of NPC led to expression and secretion of IFN-β, IL-28A/IL-28B and IL-29, which mediated an antiviral state against HCV. Disclosures: The following people have nothing to disclose: Melanie Lutterbeck, Ruth Broering, Kathrin buy Ibrutinib Kleinehr, Andreas Paul, Guido Gerken, Joerg F. Schlaak Background: Affecting an estimated 200 million people globally, HCV is the world’s most common blood-borne viral infection for which there is no vaccine. In the U.S. alone, over 40,000 births occur annually in HCV-positive pregnant women. HCV infection has recently been identified as an independent risk factor for pre-term delivery, perinatal mortality, intrauterine growth restriction, and other complications. However, the rate of HCV transmission to the fetus is <5%, suggesting potent antiviral responses within the maternal-fetal interface. Methods: Cytotrophoblasts and villous explants were isolated

from elective terminations of normal pregnancies (first and second trimester). Primary trophoblasts and a first trimester trophoblast cell line were comprehensively phenotyped by Flow cytometry. The antiviral responses were analysed by qRT-PCR after stimulating the cells with an HCV-specific medchemexpress PAMP (the non-activating HCV X-region was used as a control). Cytokine and chemokine production upon HCV PAMP activation was detected by ELISA and Luminex assays. Results:

Primary trophoblasts (n = 7) and the trophoblast cell line and constitutively express the HCV receptors CD81, LDL-R, SR-BI, as well as other relevant markers used to confirm trophoblast purity, including cytokeratin 7, C-erb2 and EGFR. HCV PAMP induces robust and broad type I and III IFNs (IFNα1, IFNα2, IFNβ, IL-28A, IL-28B, IL-29) whereas TLR3 induced a modest increase in IFN-β but not induce significant Type III IFNs (IFNLs). Furthermore, HCV PAMP upregulated multiple chemokine genes in both the cell line and primary trophoblasts; high levels of secreted chemokines (IL-8, MCP-1α, MIP-1, fractalkine, RANTES, and IP-10) were confirmed in the supernatants of PAMP-transfected trophoblasts. Trophoblasts transfected with HCV PAMP also demonstrated increased expression of HLA-E, known to be a ligand for NK and gamma-delta T cells. HCV PAMP transfection increased Annexin V and active caspase 3 expression, consistent with a pro-apoptotic response within trophoblasts.