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

  • Vinicius Kannen
  • Juliana Y. Sakita
  • Zumira A. Carneiro
  • Michael Bader
  • Natalia Alenina
  • Regina R. Teixeira
  • Enio C. de Oliveira
  • Mariângela O. Brunaldi
  • Bianca Gasparotto
  • Daniela C. Sartori
  • Cleverson R. Fernandes
  • João S. Silva
  • Marcus V. Andrade
  • Wilson A. SilvaJr.
  • Sergio A. Uyemura
  • Sérgio B. Garcia
Original Article
  • 73 Downloads

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.

Keywords

Neuroendocrine system Enteric neurons Parasites Intestines 

Notes

Acknowledgments

The authors also disclose receipt of the following financial support for the development of this investigation: the National Council for Scientific and Technological Development (CNPQ; 443376/2014-0), Sao Paulo Research Foundation (FAPESP; 2014/06428-5), and Russian Science Foundation (No. 14-50-00069). The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.

Author's contribution

Study concept and design: VK and SBG. Acquisition of data: BG, JYS, NA, MB, RRT, ECO, DCS, JSS, MVA, CRF, ZAC, SAU. Statistical analysis: VK and SBG. Analysis and interpretation of data: VK and SBG. Drafting of the manuscript: All. Critical revision of the manuscript: All. Obtained funding: VK. Technical and material support: SAU, NA, MB, ECO, ZAC, DCS, MVA, SBG. Study supervision: SBG.

Compliance with ethical standards

Conflict of interest

All authors have no conflicts of interest to disclose.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • 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. SilvaJr.
    • 10
  • Sergio A. Uyemura
    • 1
  • Sérgio B. Garcia
    • 2
  1. 1.Department of Toxicology, Bromatology, and Clinical AnalysisUniversity of Sao PauloRibeirão PretoBrazil
  2. 2.Department of PathologyUniversity of Sao PauloRibeirão PretoBrazil
  3. 3.Max Delbrück Center for Molecular MedicineBerlinGermany
  4. 4.Charité University Medicine BerlinBerlinGermany
  5. 5.Berlin Institute of Health (BIH)BerlinGermany
  6. 6.Institute of Translational Biomedicine, St. Petersburg State UniversitySt. PetersburgRussia
  7. 7.Department of SurgeryFederal University of GoiasGoiâniaBrazil
  8. 8.Department of Biochemistry and ImmunologyUniversity of São PauloRibeirão PretoBrazil
  9. 9.Department of Clinical MedicineFederal University of Minas GeraisBelo HorizonteBrazil
  10. 10.Department of GeneticsUniversity of Sao PauloRibeirão PretoBrazil

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