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dc.contributor.authorSteel, Nicola
dc.contributor.authorFaniyi, Aduragbemi A
dc.contributor.authorRahman, Sayema
dc.contributor.authorSwietlik, Stefanie
dc.contributor.authorCzajkowska, Beata I
dc.contributor.authorChan, Bethany T
dc.contributor.authorHardgrave, Alexander
dc.contributor.authorSteel, Anthony
dc.contributor.authorSparwasser, Tim D
dc.contributor.authorAssas, Mushref B
dc.contributor.authorGrencis, Richard K
dc.contributor.authorTravis, Mark A
dc.contributor.authorWorthington, John J
dc.date.accessioned2019-05-10T12:39:09Z
dc.date.available2019-05-10T12:39:09Z
dc.date.issued2019-01-01
dc.identifier.citationPLoS Pathog. 2019 Apr 18;15(4):e1007657. doi: 10.1371/journal.ppat.1007657. eCollection 2019 Apr.en_US
dc.identifier.issn1553-7374
dc.identifier.pmid30998782
dc.identifier.doi10.1371/journal.ppat.1007657
dc.identifier.urihttp://hdl.handle.net/10033/621768
dc.description.abstractHelminths are highly prevalent metazoan parasites that infect over a billion of the world’s population. Hosts have evolved numerous mechanisms to drive the expulsion of these parasites via Th2-driven immunity, but these responses must be tightly controlled to prevent equally devastating immunopathology. However, mechanisms that regulate this balance are still unclear. Here we show that the vigorous Th2 immune response driven by the small intestinal helminth Trichinella spiralis, is associated with increased TGFβ signalling responses in CD4+ T-cells. Mechanistically, enhanced TGFβ signalling in CD4+ T-cells is dependent on dendritic cell-mediated TGFβ activation which requires expression of the integrin αvβ8. Importantly, mice lacking integrin αvβ8 on DCs had a delayed ability to expel a T. spiralis infection, indicating an important functional role for integrin αvβ8-mediated TGFβ activation in promoting parasite expulsion. In addition to maintaining regulatory T-cell responses, the CD4+ T-cell signalling of this pleiotropic cytokine induces a Th17 response which is crucial in promoting the intestinal muscle hypercontractility that drives worm expulsion. Collectively, these results provide novel insights into intestinal helminth expulsion beyond that of classical Th2 driven immunity, and highlight the importance of IL-17 in intestinal contraction which may aid therapeutics to numerous diseases of the intestine.en_US
dc.language.isoenen_US
dc.publisherPLOSen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleTGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice.en_US
dc.typeArticleen_US
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen-Str.7,30625 Hannover, Germany.en_US
dc.identifier.journalPLoS pathogensen_US
refterms.dateFOA2019-05-10T12:39:10Z
dc.source.journaltitlePLoS pathogens


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