Haeme oxygenase activity protects the host against excessive cardiac inflammation during experimental Trypanosoma cruzi infection

• Published in: Microbes and infection Vol. 16; no. 1; pp. 28 - 39
• Main Authors: Gutierrez, Fredy R.S., Pavanelli, Wander R., Medina, Tiago S., Silva, Grace K., Mariano, Flávia S., Guedes, Paulo M.M., Mineo, Tiago W.P., Rossi, Marcos A., Cunha, Fernando Q., Silva, João S.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.01.2014
• Subjects: Animals; Chagas Cardiomyopathy - immunology; Chagas Cardiomyopathy - metabolism; Chagas Cardiomyopathy - parasitology; Chagas Cardiomyopathy - pathology; Cytokines - metabolism; Disease Models, Animal; Enzyme Activation - drug effects; Female; Haeme oxygenase; Heme Oxygenase-1 - metabolism; Hemin - administration & dosage; Hemin - pharmacology; Inflammation - metabolism; Inflammation - pathology; Mice; Nitric Oxide - biosynthesis; Protoporphyrins - administration & dosage; Protoporphyrins - pharmacology; Regulatory T cells; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Trypanosoma cruzi; Regulatory T cells; Haeme oxygenase; Trypanosoma cruzi
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2013.10.007

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.