TGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice.

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 immunop...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nicola Steel, Aduragbemi A Faniyi, Sayema Rahman, Stefanie Swietlik, Beata I Czajkowska, Bethany T Chan, Alexander Hardgrave, Anthony Steel, Tim D Sparwasser, Mushref B Assas, Richard K Grencis, Mark A Travis, John J Worthington
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2019
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4df84396880e471badbb38cffcabcad0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4df84396880e471badbb38cffcabcad0
record_format	dspace
spelling	oai:doaj.org-article:4df84396880e471badbb38cffcabcad02021-12-02T19:59:40ZTGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice.1553-73661553-737410.1371/journal.ppat.1007657https://doaj.org/article/4df84396880e471badbb38cffcabcad02019-04-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1007657https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Helminths 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.Nicola SteelAduragbemi A FaniyiSayema RahmanStefanie SwietlikBeata I CzajkowskaBethany T ChanAlexander HardgraveAnthony SteelTim D SparwasserMushref B AssasRichard K GrencisMark A TravisJohn J WorthingtonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 15, Iss 4, p e1007657 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Nicola Steel Aduragbemi A Faniyi Sayema Rahman Stefanie Swietlik Beata I Czajkowska Bethany T Chan Alexander Hardgrave Anthony Steel Tim D Sparwasser Mushref B Assas Richard K Grencis Mark A Travis John J Worthington TGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice.
description	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.
format	article
author	Nicola Steel Aduragbemi A Faniyi Sayema Rahman Stefanie Swietlik Beata I Czajkowska Bethany T Chan Alexander Hardgrave Anthony Steel Tim D Sparwasser Mushref B Assas Richard K Grencis Mark A Travis John J Worthington
author_facet	Nicola Steel Aduragbemi A Faniyi Sayema Rahman Stefanie Swietlik Beata I Czajkowska Bethany T Chan Alexander Hardgrave Anthony Steel Tim D Sparwasser Mushref B Assas Richard K Grencis Mark A Travis John J Worthington
author_sort	Nicola Steel
title	TGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice.
title_short	TGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice.
title_full	TGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice.
title_fullStr	TGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice.
title_full_unstemmed	TGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice.
title_sort	tgfβ-activation by dendritic cells drives th17 induction and intestinal contractility and augments the expulsion of the parasite trichinella spiralis in mice.
publisher	Public Library of Science (PLoS)
publishDate	2019
url	https://doaj.org/article/4df84396880e471badbb38cffcabcad0
work_keys_str_mv	AT nicolasteel tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice AT aduragbemiafaniyi tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice AT sayemarahman tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice AT stefanieswietlik tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice AT beataiczajkowska tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice AT bethanytchan tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice AT alexanderhardgrave tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice AT anthonysteel tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice AT timdsparwasser tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice AT mushrefbassas tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice AT richardkgrencis tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice AT markatravis tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice AT johnjworthington tgfbactivationbydendriticcellsdrivesth17inductionandintestinalcontractilityandaugmentstheexpulsionoftheparasitetrichinellaspiralisinmice
_version_	1718375720254701568

TGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice.

Ejemplares similares