Vol.:(0123456789) 1 3 Digestive Diseases and Sciences https://doi.org/10.1007/s10620-018-5015-6 ORIGINAL ARTICLE Mast Cells and Serotonin Synthesis Modulate Chagas Disease in the Colon: Clinical and Experimental Evidence Vinicius Kannen 1,2  · Juliana Y. Sakita 1  · Zumira A. Carneiro 1  · Michael Bader 3,4,5  · Natalia Alenina 3,6  · Regina R. Teixeira 1  · Enio C. de Oliveira 7  · Mariângela O. Brunaldi 2  · Bianca Gasparotto 1  · Daniela C. Sartori 8  · Cleverson R. Fernandes 2  · João S. Silva 8  · Marcus V. Andrade 9  · Wilson A. Silva Jr. 10  · Sergio A. Uyemura 1  · Sérgio B. Garcia 2 Received: 5 October 2016 / Accepted: 7 March 2018 © Springer Science+Business Media, LLC, part of Springer Nature 2018 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 parafn-embedded samples from normal colon and chagasic megacolon were histo- pathologically 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 diferent 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 signifcantly increase parasitemia in the colon (p > 0.05), rescu- ing its synthesis promoted trypanosomiasis (p < 0.01). T. cruzi-related 5-HT release (p < 0.05) seemed not only to increase infammatory 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 fnding 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 * Vinicius Kannen vinicius.kannen@fcfrp.usp.br 1 Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirão Preto 14040-903, Brazil 2 Department of Pathology, University of Sao Paulo, Ribeirão Preto, Brazil 3 Max Delbrück Center for Molecular Medicine, Berlin, Germany 4 Charité University Medicine Berlin, Berlin, Germany 5 Berlin Institute of Health (BIH), Berlin, Germany 6 Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia 7 Department of Surgery, Federal University of Goias, Goiânia, Brazil 8 Department of Biochemistry and Immunology, University of São Paulo, Ribeirão Preto, Brazil 9 Department of Clinical Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil 10 Department of Genetics, University of Sao Paulo, Ribeirão Preto, Brazil