5-lipoxygenase is a key determinant of acute myocardial inflammation and mortality during Trypanosoma cruzi infection.
This study provides evidence supporting the idea that although inflammatory cells migration to the cardiac tissue is necessary to control the growth of Trypanosoma cruzi, the excessive influx of such cells during acute myocarditis may be deleterious to the host. Production of lipid mediators of inflammation like leukotrienes (LTs) along with cytokines and chemokines largely influences the severity of inflammatory injury in response to tissue parasitism. T. cruzi infection in mice deficient in 5-lipoxygenase (5-LO), the enzyme responsible for the synthesis of LTs and other lipid inflammatory mediators, resulted in transiently increased parasitemia, and improved survival rate compared with WT mice. Myocardia from 5-LO(-/-) mice exhibited reduced inflammation, collagen deposition, and migration of CD4(+), CD8(+), and IFN-gamma-producer cells compared with WT littermates. Moreover, decreased amounts of TNF-alpha, IFN-gamma, and nitric oxide synthase were found in the hearts of 5-LO(-/-) mice. Interestingly, despite of early higher parasitic load, 5-LO(-/-) mice survived, and controlled T. cruzi infection. These results show that efficient parasite clearance is possible in a context of moderate inflammatory response, as occurred in 5-LO(-/-) mice, in which reduced myocarditis protects the animals during T. cruzi infection.
Pavanelli
Wander R
WR
Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.
Gutierrez
Fredy R S
FR
Mariano
Flávia S
FS
Prado
Cibele M
CM
Ferreira
Beatriz Rossetti
BR
Teixeira
Mauro Martins
MM
Canetti
Cláudio
C
Rossi
Marcos A
MA
Cunha
Fernando Q
FQ
Silva
João S
JS
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism*; D002598:Chagas Cardiomyopathy / Q000276:immunology / Q000401:mortality / Q000469:parasitology* / Q000473:pathology*; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D015289:Leukotrienes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology; D018512:Parasitemia / Q000276:immunology; D016019:Survival Analysis; D014349:Trypanosoma cruzi / Q000276:immunology / Q000472:pathogenicity*
D016207:Cytokines; D018836:Inflammation Mediators; D015289:Leukotrienes; D001094:Arachidonate 5-Lipoxygenase