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-KitW-sh mice underwent T. cruzi infection together with their wild-type counterparts. Also, mice underwent different drug treatments (16.1.1064.60.3).
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).
We show that mast cells may modulate the T. cruzi-related increase of 5-HT synthesis in the intestinal colon.
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The authors also disclose receipt of the following financial support for the development of this investigation: the National Council for Scientific and Technological Development (CNPQ; 443376/2014-0), Sao Paulo Research Foundation (FAPESP; 2014/06428-5), and Russian Science Foundation (No. 14-50-00069). The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.
Conflict of interest
All authors have no conflicts of interest to disclose.
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Kannen, V., Sakita, J.Y., Carneiro, Z.A. et al. Mast Cells and Serotonin Synthesis Modulate Chagas Disease in the Colon: Clinical and Experimental Evidence. Dig Dis Sci 63, 1473–1484 (2018). https://doi.org/10.1007/s10620-018-5015-6
- Neuroendocrine system
- Enteric neurons