1. Mast Cells and Serotonin Synthesis Modulate Chagas Disease in the Colon: Clinical and Experimental Evidence.
- Author
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Kannen V, Sakita JY, Carneiro ZA, Bader M, Alenina N, Teixeira RR, de Oliveira EC, Brunaldi MO, Gasparotto B, Sartori DC, Fernandes CR, Silva JS, Andrade MV, Silva WA Jr, Uyemura SA, and Garcia SB
- Subjects
- Adult, Aged, Animals, Case-Control Studies, Chagas Disease genetics, Chagas Disease parasitology, Colon parasitology, Host-Pathogen Interactions, Humans, Intestinal Diseases, Parasitic genetics, Intestinal Diseases, Parasitic parasitology, Male, Mast Cells parasitology, Megacolon genetics, Megacolon parasitology, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Proto-Oncogene Proteins c-kit genetics, Proto-Oncogene Proteins c-kit metabolism, Time Factors, Tryptophan Hydroxylase genetics, Tryptophan Hydroxylase metabolism, Chagas Disease metabolism, Colon metabolism, Intestinal Diseases, Parasitic metabolism, Mast Cells metabolism, Megacolon metabolism, Serotonin biosynthesis, Trypanosoma cruzi pathogenicity
- Abstract
Background: Trypanosoma cruzi (T. cruzi) infects millions of Latin Americans each year and can induce chagasic megacolon. Little is known about how serotonin (5-HT) modulates this condition. Aim We investigated whether 5-HT synthesis alters T. cruzi infection in the colon., Materials and Methods: Forty-eight paraffin-embedded samples from normal colon and chagasic megacolon were histopathologically analyzed (173/2009). Tryptophan hydroxylase 1 (Tph1) knockout (KO) mice and c-Kit
W-sh mice underwent T. cruzi infection together with their wild-type counterparts. Also, mice underwent different drug treatments (16.1.1064.60.3)., Results: In both humans and experimental mouse models, the serotonergic system was activated by T. cruzi infection (p < 0.05). While treating Tph1KO mice with 5-HT did not significantly increase parasitemia in the colon (p > 0.05), rescuing its synthesis promoted trypanosomiasis (p < 0.01). T. cruzi-related 5-HT release (p < 0.05) seemed not only to increase inflammatory signaling, but also to enlarge the pericryptal macrophage and mast cell populations (p < 0.01). Knocking out mast cells reduced trypanosomiasis (p < 0.01), although it did not further alter the neuroendocrine cell number and Tph1 expression (p > 0.05). Further experimentation revealed that pharmacologically inhibiting mast cell activity reduced colonic infection (p < 0.01). A similar finding was achieved when 5-HT synthesis was blocked in c-KitW-sh mice (p > 0.05). However, inhibiting mast cell activity in Tph1KO mice increased colonic trypanosomiasis (p < 0.01)., Conclusion: We show that mast cells may modulate the T. cruzi-related increase of 5-HT synthesis in the intestinal colon.- Published
- 2018
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