title: The Aryl Hydrocarbon Receptor Modulates Production of Cytokines and Reactive Oxygen Species and Development of Myocarditis during Trypanosoma cruzi Infection.
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.
authors.affiliation: Program in Health Sciences: Infectious Diseases and Tropical Medicine, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Andréia
authors.initials: A
authors.lastname: Barroso
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Melisa
authors.initials: M
authors.lastname: Gualdrón-López
authors.affiliation: Program in Health Sciences: Infectious Diseases and Tropical Medicine, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Lísia
authors.initials: L
authors.lastname: Esper
authors.affiliation: Program in Health Sciences: Infectious Diseases and Tropical Medicine, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Fátima
authors.initials: F
authors.lastname: Brant
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Ronan R S
authors.initials: RR
authors.lastname: Araújo
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Matheus B H
authors.initials: MB
authors.lastname: Carneiro
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Thiago V
authors.initials: TV
authors.lastname: Ávila
authors.affiliation: Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Danielle G
authors.initials: DG
authors.lastname: Souza
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Leda Q
authors.initials: LQ
authors.lastname: Vieira
authors.affiliation: Department of Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Milene A
authors.initials: MA
authors.lastname: Rachid
authors.affiliation: Departments of Pathology and Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Tanowitz
authors.affiliation: Program in Health Sciences: Infectious Diseases and Tropical Medicine, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Program in Health Sciences: Infectious Diseases and Tropical Medicine, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil machadofs@icb.ufmg.br.
authors.forename: Fabiana S
authors.initials: FS
authors.lastname: Machado
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000378:metabolism / Q000473:pathology; D014355:Chagas Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D009205:Myocarditis / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism / Q000502:physiology*; D013154:Spleen / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000502:physiology*
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon; D050826:Suppressor of Cytokine Signaling Proteins; D030421:Peroxynitrous Acid; D009569:Nitric Oxide