Mast Cells and Serotonin Synthesis Modulate Chagas Disease in the Colon: Clinical and Experimental Evidence

作者：Kannen Vinicius^*; Sakita Juliana Y; Carneiro Zumira A; Bader Michael; Alenina Natalia; Teixeira Regina R; de Oliveira Enio C; Brunaldi Mariangela O; Gasparotto Bianca; Sartori Daniela C; Fernandes Cleverson R; Silva Joao S; Andrade Marcus V; Silva Wilson A; Uyemura Sergio A; Garcia Sergio B

来源：Digestive Diseases and Sciences, 2018, 63(6): 1473-1484.

DOI：10.1007/s10620-018-5015-6

• Neuroendocrine system
• Enteric neurons
• Parasites
• Intestines

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.

• 出版日期2018-6