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Mast cells and serotonin synthesis modulate Chagas disease in the colon: clinical and experimental evidence

Item Type:Article
Title:Mast cells and serotonin synthesis modulate Chagas disease in the colon: clinical and experimental evidence
Creators Name:Kannen, V. and Sakita, J.Y. and Carneiro, Z.A. and Bader, M. and Alenina, N. and Teixeira, R.R. and de Oliveira, E.C. and Brunaldi, M.O. and Gasparotto, B. and Sartori, D.C. and Fernandes, C.R. and Silva, J.S. and Andrade, M.V. and Silva, W.A. and Uyemura, S.A. and Garcia, S.B.
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-Kit(W-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.
Keywords:Neuroendocrine System, Enteric Neurons, Parasites, Intestines, Animals, Mice
Source:Digestive Diseases and Sciences
Page Range:1473-1484
Date:June 2018
Official Publication:https://doi.org/10.1007/s10620-018-5015-6
PubMed:View item in PubMed

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