The Substance P Receptor Is Necessary for a Normal Granulomatous Response in Murine Schistosomiasis Mansoni

Abstract

Immune cells within the granulomas of murine schistosomiasis mansoni make the neuropeptide substance P (SP) and express neurokine 1 receptor, which is the specific receptor for substance P (SPr). It was determined if mice with deletion of the SPr (SPr−/−) would develop a normal granulomatous response to schistosome ova during the course of natural infection. Mean liver granuloma size was smaller in SPr−/− mice compared with that of wild-type control animals. Although flow analysis revealed little difference in the cellular composition of the granulomas, both splenocytes and granuloma cells from SPr−/− mice produced much less IFN-γ and IgG2a and less IgE. The expression of Th2 cytokines (IL-4/IL-5) and IgG1 was comparable to the wild-type control. The mouse with targeted disruption of its SPr had the nonmammalian gene encoding the enzyme β-galactosidase inserted in exon 1 of the SPr gene. There was β-galactosidase activity in many mononuclear cells scattered throughout the schistosome granulomas of SPr−/− mice. Also, a granuloma T cell line derived from this transgenic mouse produced β-galactosidase. These results provide further evidence that in murine schistosomiasis SPr is displayed commonly on granuloma inflammatory cells and is important for granuloma development and expression of IFN-γ circuitry in this natural infection.