title: Interleukin-13 Receptor α1-Dependent Responses in the Intestine Are Critical to Parasite Clearance.
abstract: Nematode infection upregulates interleukin-4 (IL-4) and IL-13 and induces STAT6-dependent changes in gut function that promote worm clearance. IL-4 and IL-13 activate the type 2 IL-4 receptor (IL-4R), which contains the IL-13Rα1 and IL-4Rα chains. We used mice deficient in IL-13Rα1 (IL-13Rα1(-/-)) to examine the contribution of IL-13 acting at the type 2 IL-4R to immune and functional responses to primary (Hb1) and secondary (Hb2) infections with the gastrointestinal nematode parasite Heligmosomoides bakeri There were differences between strains in the IL-4 and IL-13 expression responses to Hb1 but not Hb2 infection. Following Hb2 infection, deficient mice had impaired worm expulsion and higher worm fecundity despite normal production of Th2-derived cytokines. The upregulation of IL-25 and IL-13Rα2 in Hb1- and Hb2-infected wild-type (WT) mice was absent in IL-13Rα1(-/-)mice. Goblet cell numbers and resistin-like molecule beta (RELM-β) expression were attenuated significantly in IL-13Rα1(-/-)mice following Hb2 infections. IL-13Rα1 contributes to the development of alternatively activated macrophages, but the type 1 IL-4R is also important. Hb1 infection had no effects on smooth muscle function or epithelial permeability in either strain, while the enhanced mucosal permeability and changes in smooth muscle function and morphology observed in response to Hb2 infection in WT mice were absent in IL-13Rα1(-/-)mice. Notably, the contribution of claudin-2, which has been linked to IL-13, does not mediate the increased mucosal permeability following Hb2 infection. These results show that activation of IL-13Rα1 is critical for key aspects of the immune and functional responses to Hb2 infection that facilitate expulsion.
authors.affiliation: Departments of Radiation Oncology and Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Rex
authors.initials: R
authors.lastname: Sun
authors.affiliation: U.S. Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, Maryland, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Urban
authors.affiliation: Departments of Radiation Oncology and Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Notari
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Vanuytsel
authors.affiliation: Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: Kathleen B
authors.initials: KB
authors.lastname: Madden
authors.affiliation: Departments of Radiation Oncology and Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Bohl
authors.affiliation: Division of Parasitology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Thirumalai R
authors.initials: TR
authors.lastname: Ramalingam
authors.affiliation: Division of Parasitology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Wynn
authors.affiliation: Departments of Radiation Oncology and Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Aiping
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Departments of Radiation Oncology and Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA tdonohue@mbrc.umaryland.edu.
authors.forename: Terez
authors.initials: T
authors.lastname: Shea-Donohue
mesh_terms: D000818:Animals; D005260:Female; D006369:Heligmosomatoidea; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000235:genetics / Q000378:metabolism*; D007411:Intestinal Diseases, Parasitic / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology
chemical_list: D053661:Interleukin-13 Receptor alpha1 Subunit
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