title: IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  First, 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-gamma and TNF-alpha and enhanced specific type 1 chemokine and chemokine receptors expression. Moreover, the results showed that IL-17 regulates T-bet, RORgammat and STAT-3 expression in the heart, showing that IL-17 controls the differentiation of Th1 cells in infected mice.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Biochemistry and immunology, School of Medicine at Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Paulo Marcos
authors.initials: PM
authors.lastname: da Matta Guedes
authors.forename: Fredy R S
authors.initials: FR
authors.lastname: Gutierrez
authors.forename: Flavia L
authors.initials: FL
authors.lastname: Maia
authors.forename: Cristiane M
authors.initials: CM
authors.lastname: Milanezi
authors.forename: Grace K
authors.initials: GK
authors.lastname: Silva
authors.forename: Wander R
authors.initials: WR
authors.lastname: Pavanelli
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000473:pathology*; D005260:Female; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D020381:Interleukin-17