Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4Ralpha-deficient mice

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dc.contributor.authorHorsnell, William G Cen_ZA
dc.contributor.authorCutler, Antony Jen_ZA
dc.contributor.authorHoving, J Claireen_ZA
dc.contributor.authorMearns, Helenen_ZA
dc.contributor.authorMyburgh, Elmarieen_ZA
dc.contributor.authorArendse, Bereniceen_ZA
dc.contributor.authorFinkelman, Fred Den_ZA
dc.contributor.authorOwens, Gary Ken_ZA
dc.contributor.authorErle, Daveen_ZA
dc.contributor.authorBrombacher, Franken_ZA
dc.date.accessioned2015-11-23T12:35:25Z
dc.date.available2015-11-23T12:35:25Z
dc.date.issued2007en_ZA
dc.description.abstractInterleukin 4 receptor α (IL-4Rα) is essential for effective clearance of gastrointestinal nematode infections. Smooth muscle cells are considered to play a role in the type 2 immune response-driven expulsion of gastrointestinal nematodes. Previous studies have shown in vitro that signal transducer and activator of transcription 6 signaling in response to parasitic nematode infection significantly increases smooth muscle cell contractility. Inhibition of the IL-4Rα pathway inhibits this response. How this response manifests itself in vivo is unknown. In this study, smooth muscle cell IL-4Rα-deficient mice (SM-MHC Cre IL-4Rα −/lox ) were generated and characterized to uncover any role for IL-4/IL-13 in this non-immune cell type in response to Nippostrongylus brasiliensis infection. IL-4Rα was absent from α-actin-positive smooth muscle cells, while other cell types showed normal IL-4Rα expression, thus demonstrating efficient cell-type-specific deletion of the IL-4Rα gene. N. brasiliensis -infected SM-MHC Cre IL-4Rα −/lox mice showed delayed ability to resolve infection with significantly prolonged fecal egg recovery and delayed worm expulsion. The delayed expulsion was related to a delayed intestinal goblet cell hyperplasia, reduced T helper 2 cytokine production in the mesenteric lymph node, and reduced M3 muscarinic receptor expression during infection. Together, these results demonstrate that in vivo IL-4Rα-responsive smooth muscle cells are beneficial for N. brasiliensis expulsion by coordinating T helper 2 cytokine responses, goblet hyperplasia, and acetylcholine responsiveness, which drive smooth muscle cell contractions.en_ZA
dc.identifier.apacitationHorsnell, W. G. C., Cutler, A. J., Hoving, J. C., Mearns, H., Myburgh, E., Arendse, B., ... Brombacher, F. (2007). Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4Ralpha-deficient mice. <i>PLoS One</i>, http://hdl.handle.net/11427/15328en_ZA
dc.identifier.chicagocitationHorsnell, William G C, Antony J Cutler, J Claire Hoving, Helen Mearns, Elmarie Myburgh, Berenice Arendse, Fred D Finkelman, Gary K Owens, Dave Erle, and Frank Brombacher "Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4Ralpha-deficient mice." <i>PLoS One</i> (2007) http://hdl.handle.net/11427/15328en_ZA
dc.identifier.citationHorsnell, W. G., Cutler, A. J., Hoving, J. C., Mearns, H., Myburgh, E., Arendse, B., ... & Brombacher, F. (2007). Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4Ralpha-deficient mice. PLoS pathog, 3(1), e1. doi:10.1371/journal.ppat.0030001en_ZA
dc.identifier.ris TY - Journal Article AU - Horsnell, William G C AU - Cutler, Antony J AU - Hoving, J Claire AU - Mearns, Helen AU - Myburgh, Elmarie AU - Arendse, Berenice AU - Finkelman, Fred D AU - Owens, Gary K AU - Erle, Dave AU - Brombacher, Frank AB - Interleukin 4 receptor α (IL-4Rα) is essential for effective clearance of gastrointestinal nematode infections. Smooth muscle cells are considered to play a role in the type 2 immune response-driven expulsion of gastrointestinal nematodes. Previous studies have shown in vitro that signal transducer and activator of transcription 6 signaling in response to parasitic nematode infection significantly increases smooth muscle cell contractility. Inhibition of the IL-4Rα pathway inhibits this response. How this response manifests itself in vivo is unknown. In this study, smooth muscle cell IL-4Rα-deficient mice (SM-MHC Cre IL-4Rα −/lox ) were generated and characterized to uncover any role for IL-4/IL-13 in this non-immune cell type in response to Nippostrongylus brasiliensis infection. IL-4Rα was absent from α-actin-positive smooth muscle cells, while other cell types showed normal IL-4Rα expression, thus demonstrating efficient cell-type-specific deletion of the IL-4Rα gene. N. brasiliensis -infected SM-MHC Cre IL-4Rα −/lox mice showed delayed ability to resolve infection with significantly prolonged fecal egg recovery and delayed worm expulsion. The delayed expulsion was related to a delayed intestinal goblet cell hyperplasia, reduced T helper 2 cytokine production in the mesenteric lymph node, and reduced M3 muscarinic receptor expression during infection. Together, these results demonstrate that in vivo IL-4Rα-responsive smooth muscle cells are beneficial for N. brasiliensis expulsion by coordinating T helper 2 cytokine responses, goblet hyperplasia, and acetylcholine responsiveness, which drive smooth muscle cell contractions. DA - 2007 DB - OpenUCT DO - 10.1371/journal.ppat.0030001 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2007 T1 - Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4Ralpha-deficient mice TI - Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4Ralpha-deficient mice UR - http://hdl.handle.net/11427/15328 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15328
dc.identifier.urihttp://dx.doi.org/10.1371/journal.ppat.0030001
dc.identifier.vancouvercitationHorsnell WGC, Cutler AJ, Hoving JC, Mearns H, Myburgh E, Arendse B, et al. Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4Ralpha-deficient mice. PLoS One. 2007; http://hdl.handle.net/11427/15328.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© 2007 Horsnell et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plospathogensen_ZA
dc.subject.otherNematode infectionsen_ZA
dc.subject.otherSmooth muscle cellsen_ZA
dc.subject.otherGastrointestinal tracten_ZA
dc.subject.otherSmooth musclesen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherMouse modelsen_ZA
dc.subject.otherMuscle contractionen_ZA
dc.subject.otherHost-pathogen interactionsen_ZA
dc.titleDelayed goblet cell hyperplasia, acetylcholine receptor expression, and worm expulsion in SMC-specific IL-4Ralpha-deficient miceen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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