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

William G C Horsnell, Antony J Cutler, Claire J Hoving, Helen Mearns, Elmarie Myburgh, Berenice Arendse, Fred D Finkelman, Gary K Owens, Dave Erle, Frank Brombacher

Research output: Contribution to journalArticlepeer-review


Interleukin 4 receptor alpha (IL-4Ralpha) 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-4Ralpha pathway inhibits this response. How this response manifests itself in vivo is unknown. In this study, smooth muscle cell IL-4Ralpha-deficient mice (SM-MHC(Cre)IL-4Ralpha(-/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-4Ralpha was absent from alpha-actin-positive smooth muscle cells, while other cell types showed normal IL-4Ralpha expression, thus demonstrating efficient cell-type-specific deletion of the IL-4Ralpha gene. N. brasiliensis-infected SM-MHC(Cre)IL-4Ralpha(-/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-4Ralpha-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.

Original languageEnglish
Pages (from-to)e1
Issue number1
Publication statusPublished - Jan 2007


  • Animals
  • Gene Expression
  • Goblet Cells/metabolism
  • Hyperplasia
  • Interleukin-4 Receptor alpha Subunit/metabolism
  • Mice
  • Muscle, Smooth/metabolism
  • Nematode Infections/immunology
  • Receptors, Cholinergic/biosynthesis

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