immunology of infectious and parasitic diseases - XXXVII Congress ...
immunology of infectious and parasitic diseases - XXXVII Congress ...
immunology of infectious and parasitic diseases - XXXVII Congress ...
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REACTIVE OXYGEN SPECIES PRODUCTION, DEVELOPMENT OF IMMUNE<br />
RESPONSE AND MYOCARDITIS DURING Trypanosoma cruzi INFECTION:<br />
EFFECTS OF ARYL HYDROCARBON RECEPTOR (AhR) ACTIVATION<br />
ANDRÉIA BARROSO (1); LISIA ESPER (1,3); FATIMA BRANT (1,3); RONAN<br />
RICARDO SABINO ARAÚJO (1); MATHEUS BATISTA HEITOR CARNEIRO<br />
(1); LEDA QUERCIA VIEIRA (1); MILENE ALVARENGA RACHID (2); FABIANA<br />
SIMÃO MACHADO (1,3)<br />
(1) Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas,<br />
Universidade Federal de Minas Gerais, Minas Gerais, Brasil. (2) Departamento<br />
de Patologia, Instituto de Ciências Biológicas, Universidade Federal de Minas<br />
Gerais, Minas Gerais, Brasil. (3) Faculdade de Medicina, Universidade Federal<br />
de Minas Gerais, Minas Gerais, Brasil.<br />
Introduction: The balance <strong>of</strong> immune response is essential to control parasite<br />
growth <strong>and</strong> pathology development during Trypanosoma cruzi infection. The 5lipoxygenase<br />
enzyme activity results in production <strong>of</strong> Lipoxin (LXA)4, an anti<br />
inflammatory eicosanoid, that is important in the regulation <strong>of</strong> inflammatory<br />
cytokines production during this infection. The role <strong>of</strong> AhR, a LXA4 nuclear<br />
receptor, during T.cruzi infection is not known.<br />
Methods <strong>and</strong> Results: Herein, wild type (WT) <strong>and</strong> AhR -/- mice were infected<br />
with T.cruzi (Y strain) <strong>and</strong> the AhR expression, parasitemia <strong>and</strong> immune<br />
response was assessed. The spleens, livers <strong>and</strong> hearts were harvested at<br />
different days post-infection (dpi) for histology or cytokines analyses by RT-PCR<br />
<strong>and</strong>/or flow cytometry. We found that during T.cruzi infection the AhR<br />
expression is up-modulated in spleen <strong>and</strong> heart. The resistance to infection is<br />
related with the absence <strong>of</strong> AhR that resulted in increased levels <strong>of</strong> IL12, IFN-γ<br />
production <strong>and</strong> number <strong>of</strong> dendritic <strong>and</strong> T cells at 10dpi.The inhibition <strong>of</strong> proinflammatory<br />
cytokine production was observed in WT, but not in AhR -/- mice,<br />
15dpi. The deficiency <strong>of</strong> AhR also resulted in an increased inflammation in the<br />
heart <strong>and</strong> liver 10dpi. In vitro, we investigated which was the mainly factor<br />
responsible for the increased efficiency to control the parasite grown in infected<br />
AhR -/- mice. We found an increased trypanocidal activity by T.cruzi-infected<br />
AhR -/- macrophages (MO), associated with increased reactive oxygen species<br />
(ROS) production, but not nitric oxide (NO) production, when compared with
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