TGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice.
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Authors
Steel, NicolaFaniyi, Aduragbemi A
Rahman, Sayema
Swietlik, Stefanie
Czajkowska, Beata I
Chan, Bethany T
Hardgrave, Alexander
Steel, Anthony
Sparwasser, Tim D
Assas, Mushref B
Grencis, Richard K
Travis, Mark A
Worthington, John J
Issue Date
2019-01-01
Metadata
Show full item recordAbstract
Helminths 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.Citation
PLoS Pathog. 2019 Apr 18;15(4):e1007657. doi: 10.1371/journal.ppat.1007657. eCollection 2019 Apr.Affiliation
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen-Str.7,30625 Hannover, Germany.Publisher
PLOSJournal
PLoS pathogensPubMed ID
30998782Type
ArticleLanguage
enISSN
1553-7374ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1007657
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- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
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