The aryl hydrocarbon receptor modulates production of cytokines and reactive oxygen species and development of myocarditis during Trypanosoma cruzi infection

Andréia Barroso, Melisa Gualdrón-López, Lísia Esper, Fátima Brant, Ronan R S Araújo, Matheus B H Carneiro, Thiago V. ávila, Danielle G. Souza, Leda Q. Vieira, Milene A. Rachid, Herbert B. Tanowitz, Mauro M. Teixeira, Fabiana S. Machado

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Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in controlling several aspects of immune responses, including the activation and differentiation of specific T cell subsets and antigen-presenting cells, thought to be relevant in the context of experimental Trypanosoma cruzi infection. The relevance of AhR for the outcome of T. cruzi infection is not known and was investigated here. We infected wild-type (WT) mice and AhR knockout (AhR KO) mice with T. cruzi (Y strain) and determined levels of parasitemia, myocardial inflammation and fibrosis, expression of AhR/cytokines/suppressor of cytokine signaling (SOCS) (spleen/heart), and production of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO-) (spleen). AhR expression was increased in the heart of infected WT mice. Infected AhR KO mice displayed significantly reduced parasitemia, inflammation, and fibrosis of the myocardium. This was associated with an anticipated increased immune response characterized by increased levels of inflammatory cytokines and reduced expression of SOCS2 and SOCS3 in the heart. In vitro, AhR deficiency caused impairment in parasite replication and decreased levels of ROS production. In conclusion, AhR influences the development of murine Chagas disease by modulating ROS production and regulating the expression of key physiological regulators of inflammation, SOCS1 to -3, associated with the production of cytokines during experimental T. cruzi infection.

Original languageEnglish (US)
Pages (from-to)3071-3082
Number of pages12
JournalInfection and Immunity
Volume84
Issue number10
DOIs
StatePublished - 2016

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Aryl Hydrocarbon Receptors
Trypanosoma cruzi
Myocarditis
Reactive Oxygen Species
Cytokines
Infection
Parasitemia
Inflammation
Fibrosis
Spleen
Peroxynitrous Acid
Chagas Disease
Viral Tumor Antigens
T-Lymphocyte Subsets
Antigen-Presenting Cells
Knockout Mice
Myocardium
Nitric Oxide
Parasites
Transcription Factors

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Barroso, A., Gualdrón-López, M., Esper, L., Brant, F., Araújo, R. R. S., Carneiro, M. B. H., ... Machado, F. S. (2016). The aryl hydrocarbon receptor modulates production of cytokines and reactive oxygen species and development of myocarditis during Trypanosoma cruzi infection. Infection and Immunity, 84(10), 3071-3082. https://doi.org/10.1128/IAI.00575-16

The aryl hydrocarbon receptor modulates production of cytokines and reactive oxygen species and development of myocarditis during Trypanosoma cruzi infection. / Barroso, Andréia; Gualdrón-López, Melisa; Esper, Lísia; Brant, Fátima; Araújo, Ronan R S; Carneiro, Matheus B H; ávila, Thiago V.; Souza, Danielle G.; Vieira, Leda Q.; Rachid, Milene A.; Tanowitz, Herbert B.; Teixeira, Mauro M.; Machado, Fabiana S.

In: Infection and Immunity, Vol. 84, No. 10, 2016, p. 3071-3082.

Research output: Contribution to journalArticle

Barroso, A, Gualdrón-López, M, Esper, L, Brant, F, Araújo, RRS, Carneiro, MBH, ávila, TV, Souza, DG, Vieira, LQ, Rachid, MA, Tanowitz, HB, Teixeira, MM & Machado, FS 2016, 'The aryl hydrocarbon receptor modulates production of cytokines and reactive oxygen species and development of myocarditis during Trypanosoma cruzi infection', Infection and Immunity, vol. 84, no. 10, pp. 3071-3082. https://doi.org/10.1128/IAI.00575-16
Barroso, Andréia ; Gualdrón-López, Melisa ; Esper, Lísia ; Brant, Fátima ; Araújo, Ronan R S ; Carneiro, Matheus B H ; ávila, Thiago V. ; Souza, Danielle G. ; Vieira, Leda Q. ; Rachid, Milene A. ; Tanowitz, Herbert B. ; Teixeira, Mauro M. ; Machado, Fabiana S. / The aryl hydrocarbon receptor modulates production of cytokines and reactive oxygen species and development of myocarditis during Trypanosoma cruzi infection. In: Infection and Immunity. 2016 ; Vol. 84, No. 10. pp. 3071-3082.
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AU - Brant, Fátima

AU - Araújo, Ronan R S

AU - Carneiro, Matheus B H

AU - ávila, Thiago V.

AU - Souza, Danielle G.

AU - Vieira, Leda Q.

AU - Rachid, Milene A.

AU - Tanowitz, Herbert B.

AU - Teixeira, Mauro M.

AU - Machado, Fabiana S.

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