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The substance P receptor is necessary for a normal granulomatous response in murine schistosomiasis mansoni
A M Blum1, A Metwali, M Kim-Miller
1Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
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-gamma 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 beta-galactosidase inserted in exon 1 of the SPr gene. There was beta-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 beta-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-gamma circuitry in this natural infection.
Insights
Mice lacking the substance P receptor (SPr) showed smaller granulomas and reduced immune responses in schistosomiasis. This indicates SPr is crucial for developing granulomas and specific immune signaling in this infection.
Area of Science:
- Immunology
- Neuroscience
- Parasitology
Background:
- Immune cells in schistosomiasis granulomas produce substance P (SP) and express its receptor, SPr.
- The role of SPr in the granulomatous response to schistosome ova is not fully understood.
Purpose of the Study:
- To investigate the role of SPr in the development of granulomas and immune responses during murine schistosomiasis mansoni infection.
Main Methods:
- Generation and analysis of SPr knockout (SPr-/-) mice infected with schistosome ova.
- Assessment of liver granuloma size, cellular composition, cytokine production (IFN-gamma, IL-4, IL-5), and immunoglobulin levels (IgG2a, IgE, IgG1).
- Utilized beta-galactosidase reporter gene in SPr-/- mice to track SPr-expressing cells.
Main Results:
- SPr-/- mice exhibited significantly smaller liver granulomas compared to wild-type controls.
- Splenocytes and granuloma cells from SPr-/- mice produced less IFN-gamma, IgG2a, and IgE.
- Th2 cytokine (IL-4/IL-5) and IgG1 expression remained comparable between SPr-/- and wild-type mice.
- Beta-galactosidase activity confirmed SPr expression on mononuclear cells within granulomas.
Conclusions:
- SPr is commonly expressed on granuloma inflammatory cells in murine schistosomiasis.
- SPr plays a significant role in granuloma development and the expression of IFN-gamma-related immune responses during this infection.