title: Haeme oxygenase activity protects the host against excessive cardiac inflammation during experimental Trypanosoma cruzi infection.
abstract: The infection with Trypanosoma cruzi induces a robust cardiac inflammation that plays a pathogenic role in the development of Chagas heart disease. In this study, we aimed at investigating the effects of Haem Oxygenase (HO) during experimental infection by T. cruzi in BALB/c and C57BL/6 mice. HO has recently emerged as a key factor modulating the immune response in diverse models of inflammatory diseases. In mice with two different genetic backgrounds, the pharmacologic inhibition of HO activity with zinc-protoporphyrin IX (ZnPPIX) induced enhanced myocarditis and reduced parasitaemia, which was accompanied by an amplified production of nitric oxide and increased influx of CD4(+), CD8(+) and IFN-γ(+) cells to the myocardium in comparison with the control group. Conversely, treatment with haemin (an activator of HO) lead to a decreased number of intracardiac CD4(+) (but not CD8(+)) cells compared to the control group. The mechanism involved in these observations is a modulation of the induction of regulatory T cells, because the stimulation or inhibition of HO was parallelled by an enhanced or reduced frequency of regulatory T cells, respectively. Hence, HO may be involved in the regulation of heart tissue inflammation and could be a potential target in conceiving future therapeutic approaches for Chagas disease.
authors.affiliation: Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia. Electronic address: fredsalazar@uan.edu.co.
authors.forename: Fredy R S
authors.initials: FR
authors.lastname: Gutierrez
authors.affiliation: Centro de Ciências Biológicas, Departamento de Ciências Patológicas, Universidade Estadual de Londrina, Brazil; Department of Biochemistry-Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
authors.forename: Wander R
authors.initials: WR
authors.lastname: Pavanelli
authors.affiliation: Department of Biochemistry-Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
authors.forename: Tiago S
authors.initials: TS
authors.lastname: Medina
authors.affiliation: Department of Biochemistry-Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
authors.forename: Grace K
authors.initials: GK
authors.lastname: Silva
authors.affiliation: Department of Biochemistry-Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
authors.forename: Flávia S
authors.initials: FS
authors.lastname: Mariano
authors.affiliation: Departamento de Microbiologia e Parasitologia, Universidade Federal do Rio Grande do Norte, Natal, Brazil; Department of Biochemistry-Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
authors.forename: Paulo M M
authors.initials: PM
authors.lastname: Guedes
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Brazil; Department of Biochemistry-Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
authors.forename: Tiago W P
authors.initials: TW
authors.lastname: Mineo
authors.affiliation: Department of Pathology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Rossi
authors.affiliation: Department of Pharmacology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: Department of Biochemistry-Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006427:Hemin / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D011524:Protoporphyrins / Q000008:administration & dosage / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014349:Trypanosoma cruzi
chemical_list: D016207:Cytokines; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D009569:Nitric Oxide; D006427:Hemin; D051547:Heme Oxygenase-1
keywords: Haeme oxygenase; Regulatory T cells; Trypanosoma cruzi