ABSTRACT
The pathology of schistosomiasis is associated with the formation of granulomas, and this process is associated with liver fibrosis. Studies indicate that Th1 cytokines reduce fibrosis in schistosomiasis, while Th2 cytokines play a part in the progression of fibrosis, and IL-13 has a critical role in this process. The IL-13Rα2 receptor, known as a 'receptor antagonist' binds with high affinity to IL-13, and studies have identified that this plays a part in reducing fibrosis and the size of granulomas. The objective of this study was to evaluate the function of IL-13Rα2 and cellular immune response in hepatic fibrosis. A negative correlation between IL-13Rα2 and IL-13 was found, suggesting an increase in cytokine in early fibrosis. Initially, a negative correlation between IFN-γ and IL-13 was found in patients without fibrosis, and subsequently, this correlation was found to be positive in patients with severe fibrosis, thereby highlighting a new mechanism for regulating the progress of periportal fibrosis. There was a positive correlation between the profiles of Th1 and Th2 cytokines, suggesting the presence of both responses, thus regulating the disease. The results contribute to a better understanding of the immune mechanisms that control the process of hepatic fibrogenesis in schistosomiasis in humans.
Subject(s)
Interleukin-13 Receptor alpha2 Subunit/immunology , Interleukin-13/immunology , Liver Cirrhosis/immunology , Liver/immunology , Schistosomiasis mansoni/immunology , Aged , Animals , Brazil , Early Diagnosis , Female , Gene Expression Regulation , Humans , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-13/genetics , Interleukin-13 Receptor alpha2 Subunit/genetics , Interleukin-2/genetics , Interleukin-2/immunology , Interleukin-4/genetics , Interleukin-4/immunology , Interleukin-6/genetics , Interleukin-6/immunology , Liver/parasitology , Liver/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/parasitology , Male , Middle Aged , Schistosoma mansoni/pathogenicity , Schistosoma mansoni/physiology , Schistosomiasis mansoni/complications , Schistosomiasis mansoni/diagnosis , Schistosomiasis mansoni/parasitology , Signal Transduction , Social Class , Th1 Cells/immunology , Th1 Cells/parasitology , Th1 Cells/pathology , Th1-Th2 Balance , Th2 Cells/immunology , Th2 Cells/parasitology , Th2 Cells/pathology , Time FactorsABSTRACT
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.