Abstract
BackgroundChagas disease is a neglected disease caused by the intracellular parasite Trypanosoma cruzi. Around 30% of the infected patients develop chronic cardiomyopathy or megasyndromes, which are high-cost morbid conditions. Immune response against myocardial self-antigens and exacerbated Th1 cytokine production has been associated with the pathogenesis of the disease. As IL-17 is involved in the pathogenesis of several autoimmune, inflammatory and infectious diseases, we investigated its role during the infection with T. cruzi.Methodology/Principal FindingsFirst, we detected significant amounts of CD4, CD8 and NK cells producing IL-17 after incubating live parasites with spleen cells from normal BALB/c mice. IL-17 is also produced in vivo by CD4+, CD8+ and NK cells from BALB/c mice on the early acute phase of infection. Treatment of infected mice with anti-mouse IL-17 mAb resulted in increased myocarditis, premature mortality, and decreased parasite load in the heart. IL-17 neutralization resulted in increased production of IL-12, IFN-γ and TNF-α and enhanced specific type 1 chemokine and chemokine receptors expression. Moreover, the results showed that IL-17 regulates T-bet, RORγt and STAT-3 expression in the heart, showing that IL-17 controls the differentiation of Th1 cells in infected mice.Conclusion/SignificanceThese results show that IL-17 controls the resistance to T. cruzi infection in mice regulating the Th1 cells differentiation, cytokine and chemokine production and control parasite-induced myocarditis, regulating the influx of inflammatory cells to the heart tissue. Correlations between the levels of IL-17, the extent of myocardial destruction, and the evolution of cardiac disease could identify a clinical marker of disease progression and may help in the design of alternative therapies for the control of chronic morbidity of chagasic patients.
Highlights
Trypanosoma cruzi is an intracellular protozoan parasite that causes Chagas’ disease, the major cause of infectious heart disease in Latin America
Chagas disease is caused by the intracellular parasite Trypanosoma cruzi
We showed by the first time that interleukin 17 (IL-17) is produced during experimental T. cruzi infection and that it plays a significant role in host defense, modulating parasiteinduced myocarditis
Summary
Trypanosoma cruzi is an intracellular protozoan parasite that causes Chagas’ disease, the major cause of infectious heart disease in Latin America. Around 10% and 20% of infected patients develop digestive (megaesophagus and megacolon) and cardiac (cardiomegaly) form of Chagas disease, respectively. The immune hyperactivity that is deleterious to the host is governed by the imbalanced production of cytokines in response to the parasite [3]. Chagas disease is a neglected disease caused by the intracellular parasite Trypanosoma cruzi. Around 30% of the infected patients develop chronic cardiomyopathy or megasyndromes, which are high-cost morbid conditions. Immune response against myocardial self-antigens and exacerbated Th1 cytokine production has been associated with the pathogenesis of the disease. As IL-17 is involved in the pathogenesis of several autoimmune, inflammatory and infectious diseases, we investigated its role during the infection with T. cruzi
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