Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice.

Gut-dwelling helminthes induce potent IL-4 and IL-13 dominated type 2 T helper cell (T(H)2) immune responses, with IL-13 production being essential for Nippostrongylus brasiliensis expulsion. This T(H)2 response results in intestinal inflammation associated with local infiltration by T cells and mac...

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Autores principales:	Saskia Schmidt, J Claire Hoving, William G C Horsnell, Helen Mearns, Antony J Cutler, Tiroyaone M Brombacher, Frank Brombacher
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0ee86013cbaf46e4a110b53ddfe17641
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spelling	oai:doaj.org-article:0ee86013cbaf46e4a110b53ddfe176412021-11-18T08:04:17ZNippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice.1932-620310.1371/journal.pone.0052211https://doaj.org/article/0ee86013cbaf46e4a110b53ddfe176412012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23284939/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Gut-dwelling helminthes induce potent IL-4 and IL-13 dominated type 2 T helper cell (T(H)2) immune responses, with IL-13 production being essential for Nippostrongylus brasiliensis expulsion. This T(H)2 response results in intestinal inflammation associated with local infiltration by T cells and macrophages. The resulting increased IL-4/IL-13 intestinal milieu drives goblet cell hyperplasia, alternative macrophage activation and smooth muscle cell hypercontraction. In this study we investigated how IL-4-promoted T cells contributed to the parasite induced effects in the intestine. This was achieved using pan T cell-specific IL-4 receptor alpha-deficient mice (iLck(cre)IL-4Rα(-/lox)) and IL-4Rα-responsive control mice. Global IL-4Rα(-/-) mice showed, as expected, impaired type 2 immunity to N. brasiliensis. Infected T cell-specific IL-4Rα-deficient mice showed comparable worm expulsion, goblet cell hyperplasia and IgE responses to control mice. However, impaired IL-4-promoted T(H)2 cells in T cell-specific IL-4Rα deficient mice led to strikingly reduced IL-4 production by mesenteric lymph node CD4(+) T cells and reduced intestinal IL-4 and IL-13 levels, compared to control mice. This reduced IL-4/IL-13 response was associated with an impaired IL-4/IL-13-mediated smooth muscle cell hypercontractility, similar to that seen in global IL-4Rα(-/-) mice. These results demonstrate that IL-4-promoted T cell responses are not required for the resolution of a primary N. brasiliensis infection. However, they do contribute significantly to an important physiological manifestation of helminth infection; namely intestinal smooth muscle cell-driven hypercontractility.Saskia SchmidtJ Claire HovingWilliam G C HorsnellHelen MearnsAntony J CutlerTiroyaone M BrombacherFrank BrombacherPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e52211 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Saskia Schmidt J Claire Hoving William G C Horsnell Helen Mearns Antony J Cutler Tiroyaone M Brombacher Frank Brombacher Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice.
description	Gut-dwelling helminthes induce potent IL-4 and IL-13 dominated type 2 T helper cell (T(H)2) immune responses, with IL-13 production being essential for Nippostrongylus brasiliensis expulsion. This T(H)2 response results in intestinal inflammation associated with local infiltration by T cells and macrophages. The resulting increased IL-4/IL-13 intestinal milieu drives goblet cell hyperplasia, alternative macrophage activation and smooth muscle cell hypercontraction. In this study we investigated how IL-4-promoted T cells contributed to the parasite induced effects in the intestine. This was achieved using pan T cell-specific IL-4 receptor alpha-deficient mice (iLck(cre)IL-4Rα(-/lox)) and IL-4Rα-responsive control mice. Global IL-4Rα(-/-) mice showed, as expected, impaired type 2 immunity to N. brasiliensis. Infected T cell-specific IL-4Rα-deficient mice showed comparable worm expulsion, goblet cell hyperplasia and IgE responses to control mice. However, impaired IL-4-promoted T(H)2 cells in T cell-specific IL-4Rα deficient mice led to strikingly reduced IL-4 production by mesenteric lymph node CD4(+) T cells and reduced intestinal IL-4 and IL-13 levels, compared to control mice. This reduced IL-4/IL-13 response was associated with an impaired IL-4/IL-13-mediated smooth muscle cell hypercontractility, similar to that seen in global IL-4Rα(-/-) mice. These results demonstrate that IL-4-promoted T cell responses are not required for the resolution of a primary N. brasiliensis infection. However, they do contribute significantly to an important physiological manifestation of helminth infection; namely intestinal smooth muscle cell-driven hypercontractility.
format	article
author	Saskia Schmidt J Claire Hoving William G C Horsnell Helen Mearns Antony J Cutler Tiroyaone M Brombacher Frank Brombacher
author_facet	Saskia Schmidt J Claire Hoving William G C Horsnell Helen Mearns Antony J Cutler Tiroyaone M Brombacher Frank Brombacher
author_sort	Saskia Schmidt
title	Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice.
title_short	Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice.
title_full	Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice.
title_fullStr	Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice.
title_full_unstemmed	Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice.
title_sort	nippostrongylus-induced intestinal hypercontractility requires il-4 receptor alpha-responsiveness by t cells in mice.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/0ee86013cbaf46e4a110b53ddfe17641
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Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice.

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