Mast Cells and Serotonin Synthesis Modulate Chagas Disease in the Colon: Clinical and Experimental Evidence
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.
KeywordsNeuroendocrine system Enteric neurons Parasites Intestines
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.
Study concept and design: VK and SBG. Acquisition of data: BG, JYS, NA, MB, RRT, ECO, DCS, JSS, MVA, CRF, ZAC, SAU. Statistical analysis: VK and SBG. Analysis and interpretation of data: VK and SBG. Drafting of the manuscript: All. Critical revision of the manuscript: All. Obtained funding: VK. Technical and material support: SAU, NA, MB, ECO, ZAC, DCS, MVA, SBG. Study supervision: SBG.
Compliance with ethical standards
Conflict of interest
All authors have no conflicts of interest to disclose.