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2 Regulates the Immune and Functional Response to Nippostrongylus brasiliensis Infection1,2
* Department of Medicine and Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, MD 21201;
Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
Diet, Genomics, & Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705
IL-13 has a prominent role in host defense against the gastrointestinal nematode Nippostrongylus brasiliensis; however, the role of IL-13R
2 in the immune and functional response to enteric infection is not known. In the current study, we investigated changes in smooth muscle and epithelial cell function as well as alterations in gene expression of IL-13 and IL-4 and their receptors using laser-capture microdissection of specific cell types in the small intestine of N. brasiliensis-infected mice. An infection-induced up-regulation of IL-13R2 gene expression was confined to smooth muscle and was dependent on STAT6 and IL-13, but not on IL-4. In contrast, expression of IL-13R1 was reduced, indicating that changes in IL-132 expression serve to limit the biological effects of IL-13. The increased availability of IL-13 in IL-13R2–/– mice resulted in marked changes in constitutive epithelial and smooth muscle function. In addition, maximal changes in smooth muscle hypercontractility and epithelial cell resistance peaked earlier after infection in IL-13R2–/– compared with wild-type mice. This did not coincide with an earlier Th2 immune response as expression of IL-4 and IL-13 was attenuated in IL-13R2–/– mice and worm expulsion was similar to that of wild-type mice. These data show that IL-13R2 plays an important role in nematode infection by limiting the availability of IL-13 during infection, thereby regulating both the immune and biological effects of IL-13.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants R01-AI/DK49316 (to T.S.-D), by U.S. Department of Agriculture CRIS Project 1235-52000-053 (to J.F.U.), by Miyagi University Overseas Research Fund (to M.M.), and by the intramural research program of National Institute of Allergy and Infectious Diseases/National Institutes of Health.
2 The opinions and assertions in this article are those of the authors and do not necessarily represent those of the U.S. Department of Agriculture or Department of Defense.
3 Current address: School of Food, Agricultural and Environmental Sciences, Miyagi University, Sendai, Miyagi, Japan 982-0215.
4 Address correspondence and reprint requests to Dr. Terez Shea-Donohue, Department of Medicine and Mucosal Biology Research Center, University School of Medicine, Baltimore, MD 21201. E-mail address: tdonohue{at}mbrc.umaryland.edu
5 Abbreviations used in this paper: LCM, laser-capture microdissection; EFS, electric field stimulation; WT, wild type; TEER, transepithelial electrical resistance.
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