IL-4R{alpha}-responsive smooth muscle cells increase intestinal hypercontractility and contribute to resistance during acute Schistosomiasis.

Interleukin-(IL)-4 and IL-13 signal through heterodimeric receptors containing a common IL-4 receptor-α (IL-4Rα) subunit, which is important for protection against helminth infections, including schistosomiasis. Previous studies demonstrated important roles for IL-4Rα-responsive hematopoietic cells, including T cells and macrophages in schistosomiasis. In this study, we examined the role of IL-4Rα responsiveness by nonhematopoietic smooth muscle cells during experimental acute murine schistosomiasis. Comparative Schistosoma mansoni infection studies with smooth muscle cell-specific IL-4Rα-deficient (SM-MHCcreIL-4Rα−/flox) mice, heterozygous control (IL-4Rα−/flox) mice, and global IL-4Rα-deficient (IL-4Rα−/−) mice were conducted. S. mansoni-infected SM-MHCcreIL-4Rα−/flox mice showed increased weight loss and earlier mortalities compared with IL-4Rα−/flox mice, despite comparable TH2/type 2 immune responses. In contrast to highly susceptible IL-4Rα-deficient mice, increased susceptibility in SM-MHCcreIL-4Rα...