TY - JOUR
T1 - Regulatory effects of IL-18 on cytokine profiles and development of myocarditis during Trypanosoma cruzi infection
AU - Esper, Lísia
AU - Utsch, Lara
AU - Soriani, Frederico M.
AU - Brant, Fátima
AU - Esteves Arantes, Rosa Maria
AU - Campos, Camila F.
AU - Pinho, Vanessa
AU - Souza, Danielle G.
AU - Teixeira, Mauro Martins
AU - Tanowitz, Herbert Bernard
AU - Vieira, Leda Quercia
AU - Machado, Fabiana Simão
N1 - Funding Information:
This work was supported by CNPq (FSM, LQV, MMT), FAPEMIG (FSM, LQV, MMT), NIH AI-076248 (HBT) and of program INCT em Dengue (Brazil).
PY - 2014/6
Y1 - 2014/6
N2 - Chagas disease, caused by Trypanosoma cruzi (Tc), is an important cause of heart disease. Resistance to Tc infection is multifactorial and associated with Th1 response. IL-18 plays an important role in regulation of IFN-γ production/development of Th1 response. However, the role of IL-18 in the setting of Tc infection remains unclear. Therefore, we investigated the role of IL-18 in the modulation of immune response and myocarditis in Tc infection. C57BL/6 and IL-18 KO mice were infected with Tc (Y or Colombian strain) and parasitemia, immune response and pathology were evaluated. Y strain infection of IL-18 KO did not alter any parameters when compared with C57BL/6 mice. However, during the acute phase (20 and 40 days post infection-dpi), Colombian strain infected-IL-18 KO mice displayed higher serum levels of IL-12 and IFN-γ, respectively, and at the chronic phase (100dpi) an increase in splenic IFN-γ-producing CD4+ and CD8+ T memory cells. There was an IL-10, FOXP3 and CD4+CD25+ cells reduction during acute infection in spleen. Additionally, there was a significant reduction in leukocyte infiltration and parasite load in myocardium of chronically infected IL-18 KO mice. Collectively, these data indicate that IL-18 contributes to the pathogenesis of Tc-induced myocarditis when infected with Colombian but not Y strain. These observations also underscore that parasite and host strain differences are important in evaluation of experimental Tc infection pathogenesis.
AB - Chagas disease, caused by Trypanosoma cruzi (Tc), is an important cause of heart disease. Resistance to Tc infection is multifactorial and associated with Th1 response. IL-18 plays an important role in regulation of IFN-γ production/development of Th1 response. However, the role of IL-18 in the setting of Tc infection remains unclear. Therefore, we investigated the role of IL-18 in the modulation of immune response and myocarditis in Tc infection. C57BL/6 and IL-18 KO mice were infected with Tc (Y or Colombian strain) and parasitemia, immune response and pathology were evaluated. Y strain infection of IL-18 KO did not alter any parameters when compared with C57BL/6 mice. However, during the acute phase (20 and 40 days post infection-dpi), Colombian strain infected-IL-18 KO mice displayed higher serum levels of IL-12 and IFN-γ, respectively, and at the chronic phase (100dpi) an increase in splenic IFN-γ-producing CD4+ and CD8+ T memory cells. There was an IL-10, FOXP3 and CD4+CD25+ cells reduction during acute infection in spleen. Additionally, there was a significant reduction in leukocyte infiltration and parasite load in myocardium of chronically infected IL-18 KO mice. Collectively, these data indicate that IL-18 contributes to the pathogenesis of Tc-induced myocarditis when infected with Colombian but not Y strain. These observations also underscore that parasite and host strain differences are important in evaluation of experimental Tc infection pathogenesis.
KW - Cytokine
KW - IL-18
KW - Myocarditis
KW - Trypanosoma cruzi
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U2 - 10.1016/j.micinf.2014.03.007
DO - 10.1016/j.micinf.2014.03.007
M3 - Article
C2 - 24704475
AN - SCOPUS:84902785175
SN - 1286-4579
VL - 16
SP - 481
EP - 490
JO - Microbes and Infection
JF - Microbes and Infection
IS - 6
ER -