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- Title
Delayed Goblet Cell Hyperplasia, Acetylcholine Receptor Expression, and Worm Expulsion in SMC-Specific IL-4Rα--Deficient Mice.
- Authors
Horsnell, William G. C.; Cutler, Antony J.; Hoving, Claire J.; Mearns, Helen; Myburgh, Elmarie; Arendse, Berenice; Finkelman, Fred D.; Owens, Gary K.; Erle, Dave; Brombacher, Frank
- Abstract
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-MHCCreIL-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-MHCCreIL-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.
- Subjects
HYPERPLASIA; EXFOLIATIVE cytology; ACETYLCHOLINE; INTERLEUKINS; IMMUNE response; NEMATODES
- Publication
PLoS Pathogens, 2007, Vol 3, Issue 1, p46
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.0030001