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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., Sakita, J.Y., Carneiro, Z.A., Bader, M., Alenina, N., Teixeira, R.R., de Oliveira, E.C., Brunaldi, M.O., Gasparotto, B., Sartori, D.C., Fernandes, C.R., Silva, J.S., Andrade, M.V., Silva, W.A., 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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