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

 

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dc.contributor.author Schmidt, Saskia en_ZA
dc.contributor.author Hoving, J Claire en_ZA
dc.contributor.author Horsnell, William G C en_ZA
dc.contributor.author Mearns, Helen en_ZA
dc.contributor.author Cutler, Antony J en_ZA
dc.contributor.author Brombacher, Tiroyaone M en_ZA
dc.contributor.author Brombacher, Frank en_ZA
dc.date.accessioned 2016-01-11T06:54:47Z
dc.date.available 2016-01-11T06:54:47Z
dc.date.issued 2012 en_ZA
dc.identifier.citation Schmidt, 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.0052211 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/16292
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0052211
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This 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.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other T cells en_ZA
dc.subject.other Gastrointestinal tract en_ZA
dc.subject.other Mouse models en_ZA
dc.subject.other Smooth muscle cells en_ZA
dc.subject.other Jejunum en_ZA
dc.subject.other Acetylcholine en_ZA
dc.subject.other Cytokines en_ZA
dc.subject.other Nematode infections en_ZA
dc.title Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2012 Schmidt et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Immunology en_ZA
uct.type.filetype Text
uct.type.filetype Image


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This 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. Except where otherwise noted, this item's license is described as This 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.