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

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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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Digestive Diseases and Sciences; v. 63, n. 6, p. 1473-1484, JUN 2018.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 14/06428-5 - Como a sinalização serotoninérgica epitelial difere dos efeitos de sua síntese neural durante a inflamação associada ou não ao câncer de cólon
• Beneficiário: Vinicius Kannen Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores