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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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Kannen, Vinicius [1, 2] ; Sakita, Juliana Y. [2] ; Carneiro, Zumira A. [2] ; Bader, Michael [3, 4, 5] ; Alenina, Natalia [4, 6] ; Teixeira, Regina R. [2] ; de Oliveira, Enio C. [7] ; Brunaldi, Mariangela O. [1] ; Gasparotto, Bianca [2] ; Sartori, Daniela C. [8] ; Fernandes, Cleverson R. [1] ; Silva, Joao S. [8] ; Andrade, Marcus V. [9] ; Silva, Wilson A. [10] ; Uyemura, Sergio A. [2] ; Garcia, Sergio B. [1]
Total Authors: 16
Affiliation:
[1] Univ Sao Paulo, Dept Pathol, Ribeirao Preto - Brazil
[2] Univ Sao Paulo, Dept Toxicol Bromatol & Clin Anal, BR-14040903 Ribeirao Preto - Brazil
[3] Charite Univ Med Berlin, Berlin - Germany
[4] Max Delbruck Ctr Mol Med, Berlin - Germany
[5] Berlin Inst Hlth, Berlin - Germany
[6] St Petersburg State Univ, Inst Translat Biomed, St Petersburg - Russia
[7] Univ Fed Goias, Dept Surg, Goiania, Go - Brazil
[8] Univ Sao Paulo, Dept Biochem & Immunol, Ribeirao Preto - Brazil
[9] Univ Fed Minas Gerais, Dept Clin Med, Belo Horizonte, MG - Brazil
[10] Univ Sao Paulo, Dept Genet, Ribeirao Preto - Brazil
Total Affiliations: 10
Document type: Journal article
Source: Digestive Diseases and Sciences; v. 63, n. 6, p. 1473-1484, JUN 2018.
Web of Science Citations: 1
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-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. (AU)

FAPESP's process: 14/06428-5 - Differentiating the effects of epithelial from the neural serotoninergic signalling during inflammation-related colon cancer
Grantee:Vinicius Kannen Cardoso
Support Opportunities: Research Grants - Young Investigators Grants