Show simple item record

dc.contributor.author David J. en_US
dc.contributor.author Clare M. en_US
dc.contributor.author Sheila en_US
dc.contributor.author James en_US
dc.contributor.author Peter M. en_US
dc.contributor.author John en_US
dc.contributor.author Sandra M. en_US
dc.date.accessioned 2011-06-03T10:15:57Z
dc.date.available 2011-06-03T10:15:57Z
dc.date.issued 2010-02 en_US
dc.identifier http://dx.doi.org/10.1128/IAI.00573-09 en_US
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 . , 10.1128/IAI.00573-09 en_US
dc.identifier.other PURE: 163511 en_US
dc.identifier.other dspace: 2160/6906 en_US
dc.identifier.uri http://hdl.handle.net/2160/6906
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_US
dc.format.extent 9 en_US
dc.relation.ispartof Infection and Immunity en_US
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_US
dc.contributor.pbl Institute of Biological, Environmental and Rural Sciences en_US


Files in this item

Files Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

Search Cadair


Advanced Search

Browse

Statistics