Major secretory antigens of the helminth Fasciola hepatica activate a suppressive dendritic cell phenotype that attenuates Th17 cells but fails to activate Th2 immune responses

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dc.contributor.author Dowling, David J.
dc.contributor.author Hamilton, Clare M.
dc.contributor.author Donnelly, Sheila
dc.contributor.author La Course, James
dc.contributor.author Brophy, Peter M.
dc.contributor.author Dalton, John
dc.contributor.author O'Neill, Sandra M.
dc.date.accessioned 2011-06-03T10:15:57Z
dc.date.available 2011-06-03T10:15:57Z
dc.date.issued 2010-02
dc.identifier.citation Dowling , D J , Hamilton , C M , Donnelly , S , La Course , J , Brophy , P M , Dalton , J & O'Neill , S M 2010 , ' Major secretory antigens of the helminth Fasciola hepatica activate a suppressive dendritic cell phenotype that attenuates Th17 cells but fails to activate Th2 immune responses ' Infection and Immunity , vol 78 , no. 2 , pp. 793-801 . en
dc.identifier.issn 1098-5522
dc.identifier.other PURE: 163511
dc.identifier.other dspace: 2160/6906
dc.identifier.uri http://hdl.handle.net/2160/6906
dc.description Dowling, D. J., Hamilton, C. M., Donnelly, S., La Course, J., Brophy, P. M., Dalton, J., O'Neill, S. M. (2010). Major secretory antigens of the helminth Fasciola hepatica activate a suppressive dendritic cell phenotype that attenuates TH17 cells but fails to activate TH2 immune responses.  Infection and Immunity, 78 (2), 793-801. IMPF: 04.09 Sponsorship: Dublin City University Faculty of Science and Health Targeted Research Development Fund, the European Union (DELIVER; grant FOOD-CT-2005-023025), and the BBSRC (grant BB/C503638/2). en
dc.description.abstract Fasciola hepatica is a helminth pathogen that drives Th2/Treg immune responses in its mammalian host. The parasite releases a large number of molecules that are critical to inducing this type of immune response. Here we have selected recombinant forms of two major F. hepatica secreted molecules, the protease cathepsin L (rFhCL1) and an antioxidant, sigma class glutathione transferase (rFhGST-si), to examine their interactions with dendritic cells (DCs). Despite enzymatic and functional differences between these molecules, both induced interleukin-6 (IL-6), IL-12p40, and macrophage inflammatory protein 2 (MIP-2) secretion from DCs and enhanced CD40 expression. While this induction was mediated by Toll-like receptor 4 (TLR4), the subsequent intracellular signaling pathways differed; rFhCL1 signaled through p38, and rFhGST-si mediated its effect via c-Jun N-terminal kinase (JNK), p38, p-NF-kappa Bp65, and IRF5. Neither rFhCL1 nor rFhGST-si enhanced DC phagocytosis or induced Th2 immune responses in vivo. However, DCs matured in the presence of either enzyme attenuated IL-17 production from OVA peptide-specific T cells in vivo. In addition, DCs exposed to either antigen secreted reduced levels of IL-23. Therefore, both F. hepatica FhCL1 and FhGST-si modulate host immunity by suppressing responses associated with chronic inflammation-an immune modulatory mechanism that may benefit the parasite's survival within the host en
dc.format.extent 9 en
dc.language.iso eng
dc.relation.ispartof Infection and Immunity en
dc.title Major secretory antigens of the helminth Fasciola hepatica activate a suppressive dendritic cell phenotype that attenuates Th17 cells but fails to activate Th2 immune responses en
dc.type Text en
dc.type.publicationtype Article (Journal) en
dc.identifier.doi http://dx.doi.org/10.1128/IAI.00573-09
dc.contributor.institution Institute of Biological, Environmental and Rural Sciences en
dc.description.status Peer reviewed en


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