IL-13 receptor alpha2 regulates the immune and functional response to Nippostrongylus brasiliensis infection

IL-13 has a prominent role in host defense against the gastrointestinal nematode Nippostrongylus brasiliensis; however, the role of IL-13Ralpha2 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-13Ralpha2 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-13Ralpha1 was reduced, indicating that changes in IL-13alpha2 expression serve to limit the biological effects of IL-13. The increased availability of IL-13 in IL-13Ralpha2(-/-) 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-13Ralpha2(-/-) 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-13Ralpha2(-/-) mice and worm expulsion was similar to that of wild-type mice. These data show that IL-13Ralpha2 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.