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

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dc.contributor.authorSchmidt, Saskiaen_ZA
dc.contributor.authorHoving, J Claireen_ZA
dc.contributor.authorHorsnell, William G Cen_ZA
dc.contributor.authorMearns, Helenen_ZA
dc.contributor.authorCutler, Antony Jen_ZA
dc.contributor.authorBrombacher, Tiroyaone Men_ZA
dc.contributor.authorBrombacher, Franken_ZA
dc.date.accessioned2016-01-11T06:54:47Z
dc.date.available2016-01-11T06:54:47Z
dc.date.issued2012en_ZA
dc.description.abstractGut-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.en_ZA
dc.identifier.apacitationSchmidt, S., Hoving, J. C., Horsnell, W. G. C., Mearns, H., Cutler, A. J., Brombacher, T. M., & Brombacher, F. (2012). Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice. <i>PLoS One</i>, http://hdl.handle.net/11427/16292en_ZA
dc.identifier.chicagocitationSchmidt, Saskia, J Claire Hoving, William G C Horsnell, Helen Mearns, Antony J Cutler, Tiroyaone M Brombacher, and Frank Brombacher "Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/16292en_ZA
dc.identifier.citationSchmidt, S., Hoving, J. C., Horsnell, W. G., Mearns, H., Cutler, A. J., Brombacher, T. M., & Brombacher, F. (2012). Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice. PLoS One, 7(12), e52211. doi:10.1371/journal.pone.0052211en_ZA
dc.identifier.ris TY - Journal Article AU - Schmidt, Saskia AU - Hoving, J Claire AU - Horsnell, William G C AU - Mearns, Helen AU - Cutler, Antony J AU - Brombacher, Tiroyaone M AU - Brombacher, Frank AB - 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. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0052211 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice TI - Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice UR - http://hdl.handle.net/11427/16292 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16292
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0052211
dc.identifier.vancouvercitationSchmidt S, Hoving JC, Horsnell WGC, Mearns H, Cutler AJ, Brombacher TM, et al. Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice. PLoS One. 2012; http://hdl.handle.net/11427/16292.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Immunologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2012 Schmidt et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherGastrointestinal tracten_ZA
dc.subject.otherMouse modelsen_ZA
dc.subject.otherSmooth muscle cellsen_ZA
dc.subject.otherJejunumen_ZA
dc.subject.otherAcetylcholineen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherNematode infectionsen_ZA
dc.titleNippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in miceen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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