IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis.
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 c...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC2821906?pdf=render |
| _version_ | 1819106348932005888 |
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| author | Paulo Marcos da Matta Guedes Fredy R S Gutierrez Flavia L Maia Cristiane M Milanezi Grace K Silva Wander R Pavanelli João S Silva |
| author_facet | Paulo Marcos da Matta Guedes Fredy R S Gutierrez Flavia L Maia Cristiane M Milanezi Grace K Silva Wander R Pavanelli João S Silva |
| author_sort | Paulo Marcos da Matta Guedes |
| collection | DOAJ |
| description | 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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. |
| first_indexed | 2024-12-22T02:36:43Z |
| format | Article |
| id | doaj.art-643f68d6e5384304936ee1f875283eb0 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-22T02:36:43Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-643f68d6e5384304936ee1f875283eb02022-12-21T18:41:44ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352010-01-0142e60410.1371/journal.pntd.0000604IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis.Paulo Marcos da Matta GuedesFredy R S GutierrezFlavia L MaiaCristiane M MilaneziGrace K SilvaWander R PavanelliJoão S SilvaBACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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.http://europepmc.org/articles/PMC2821906?pdf=render |
| spellingShingle | Paulo Marcos da Matta Guedes Fredy R S Gutierrez Flavia L Maia Cristiane M Milanezi Grace K Silva Wander R Pavanelli João S Silva IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis. PLoS Neglected Tropical Diseases |
| title | IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis. |
| title_full | IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis. |
| title_fullStr | IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis. |
| title_full_unstemmed | IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis. |
| title_short | IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis. |
| title_sort | il 17 produced during trypanosoma cruzi infection plays a central role in regulating parasite induced myocarditis |
| url | http://europepmc.org/articles/PMC2821906?pdf=render |
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