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

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dc.contributor.author Donnelly, S
dc.contributor.author O'Neill, SM
dc.contributor.author Stack, CM
dc.contributor.author Robinson, MW
dc.contributor.author Turnbull, L
dc.contributor.author Whitchurch, C
dc.contributor.author Dalton, JP
dc.date.accessioned 2011-02-07T06:20:50Z
dc.date.issued 2010-01-29
dc.identifier.citation Journal of Biological Chemistry, 2010, 285 (5), pp. 3383 - 3392
dc.identifier.issn 0021-9258
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 (FheCL1) and Schistosoma mansoni (SmCB1) protect mice from the lethal effects of lipopolysaccharide by preventing the release of inflammatory mediators, nitric oxide, interleukin-6, tumor necrosis factor α, and interleukin-12, from macrophages. The proteases specifically block the MyD88-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 of TLR3 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 of Th1 responses. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
dc.language eng
dc.relation.isbasedon 10.1074/jbc.M109.060368
dc.title Helminth cysteine proteases inhibit TRIF-dependent activation of macrophages via degradation of TLR3
dc.type Journal Article
dc.description.version Published
dc.parent Journal of Biological Chemistry
dc.journal.volume 5
dc.journal.volume 285
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 0707 Veterinary Sciences
dc.personcode 995262
dc.personcode 995261
dc.personcode 030896
dc.personcode 100777
dc.personcode 103745
dc.personcode 103744
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
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
pubs.organisational-group /University of Technology Sydney/Strength - i3
utslib.copyright.status Closed Access
utslib.copyright.date 2015-04-15 12:17:09.805752+10
pubs.consider-herdc true
utslib.collection.history School of Medical and Molecular Sciences (ID: 341)
utslib.collection.history Closed (ID: 3)

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