Helminth cysteine proteases inhibit TRIF - dependent activation of macrophages via degradation of TLR3.

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dc.contributor.author Donnelly, Sheila en_US
dc.contributor.author O'Neill, Sandra en_US
dc.contributor.author Stack, Colin en_US
dc.contributor.author Robinson, Mark en_US
dc.contributor.author Turnbull, Lynne en_US
dc.contributor.author Whitchurch, Cynthia en_US
dc.contributor.author Dalton, John en_US
dc.contributor.editor en_US
dc.date.accessioned 2011-02-07T06:20:50Z
dc.date.available 2011-02-07T06:20:50Z
dc.date.issued 2010 en_US
dc.identifier 2009001323 en_US
dc.identifier.citation Donnelly Sheila et al. 2010, 'Helminth cysteine proteases inhibit TRIF - dependent activation of macrophages via degradation of TLR3.', The American Society for Biochemistry and Molecular Biology, Inc, vol. 285, no. 5, pp. 3383-3392. en_US
dc.identifier.issn 0021-9258 en_US
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/13338
dc.description.abstract Helminth pathogens prepare a Th2 type immunological environment in their hosts to ensure their longevity. They achieve this by secreting molecules that not only actively drive type 2 responses but also suppress type 1 responses. Here, we show that the major cysteine proteases secreted from the helminth pathogens Fasciola hepatica (FheCLl) and Schistosoma mansoni (SmCBI) protect mice from the lethal effects oflipopolysaccharide by preventing the release of inflammatory mediators, nitric oxide, interleukin-6, tumor necrosis factor a, and interleukin- 12, from macro phages. The proteases specifically blocl< the MyDSS-independent TRIF-dependent signaling pathway of Toll-like receptor (TLR)4 and TLR3. Microscopical and flow cytometric studies, however, show that alteration of macrophage function by cysteine protease is not mediated by cleavage of components of the TLR4 complex on the cell surface but occurs by degradation ofTLR3 within the endosome. This is the first study to describe a parasite molecule that degrades this receptor and pinpoints a novel mechanism by which helminth parasites modulate the innate immune responses of their hosts to suppress the development ofThl responses. en_US
dc.language en_US
dc.publisher The American Society for Biochemistry and Molecular Biology, Inc en_US
dc.relation.isbasedon http://dx.doi.org/10.1074/jbc.M109.060368 en_US
dc.title Helminth cysteine proteases inhibit TRIF - dependent activation of macrophages via degradation of TLR3. en_US
dc.parent Journal Of Biological Chemistry en_US
dc.journal.volume 285 en_US
dc.journal.number 5 en_US
dc.publocation Bethesda, MA, USA en_US
dc.identifier.startpage 3383 en_US
dc.identifier.endpage 3392 en_US
dc.cauo.name SCI.Institute for Biotechnology of Infectious Diseases en_US
dc.conference Verified OK en_US
dc.for 070700 en_US
dc.personcode 995261 en_US
dc.personcode 0000021604 en_US
dc.personcode 995262 en_US
dc.personcode 100777 en_US
dc.personcode 103744 en_US
dc.personcode 103745 en_US
dc.personcode 030896 en_US
dc.percentage 100 en_US
dc.classification.name Veterinary Sciences en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US
dc.date.activity en_US
dc.location.activity en_US
dc.description.keywords NA en_US
dc.staffid 030896 en_US

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