Vinicius Kannen1,2, Juliana Y Sakita3, Zumira A Carneiro3, Michael Bader4,5,6, Natalia Alenina4,7, Regina R Teixeira3, Enio C de Oliveira8, Mariângela O Brunaldi9, Bianca Gasparotto3, Daniela C Sartori10, Cleverson R Fernandes9, João S Silva10, Marcus V Andrade11, Wilson A Silva12, Sergio A Uyemura3, Sérgio B Garcia9. 1. Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirão Preto, 14040-903, Brazil. vinicius.kannen@fcfrp.usp.br. 2. Department of Pathology, University of Sao Paulo, Ribeirão Preto, Brazil. vinicius.kannen@fcfrp.usp.br. 3. Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirão Preto, 14040-903, Brazil. 4. Max Delbrück Center for Molecular Medicine, Berlin, Germany. 5. Charité University Medicine Berlin, Berlin, Germany. 6. Berlin Institute of Health (BIH), Berlin, Germany. 7. Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia. 8. Department of Surgery, Federal University of Goias, Goiânia, Brazil. 9. Department of Pathology, University of Sao Paulo, Ribeirão Preto, Brazil. 10. Department of Biochemistry and Immunology, University of São Paulo, Ribeirão Preto, Brazil. 11. Department of Clinical Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil. 12. Department of Genetics, University of Sao Paulo, Ribeirão Preto, Brazil.
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-KitW-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-KitW-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.
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-KitW-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-KitW-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.
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