Regulatory effects of IL-18 on cytokine profiles and development of myocarditis during Trypanosoma cruzi infection.
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 (100 dpi) 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.
Department of Biochemistry and Immunology, Institute of Biological Science, Federal University of Minas Gerais, MG, Brazil; Postgraduate Program in Health Sciences: Infectious Diseases and Tropical Medicine, Medical School, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Lísia
L
Esper
Department of Biochemistry and Immunology, Institute of Biological Science, Federal University of Minas Gerais, MG, Brazil.
Lara
L
Utsch
Department of General Biology, Institute of Biological Science, Federal University of Minas Gerais, MG, Brazil.
Frederico M
FM
Soriani
Department of Biochemistry and Immunology, Institute of Biological Science, Federal University of Minas Gerais, MG, Brazil; Postgraduate Program in Health Sciences: Infectious Diseases and Tropical Medicine, Medical School, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Fátima
F
Brant
Department of Pathology, Institute of Biological Science, Federal University of Minas Gerais, MG, Brazil.
Rosa Maria
RM
Esteves Arantes
Department of Pathology, Institute of Biological Science, Federal University of Minas Gerais, MG, Brazil.
Camila F
CF
Campos
Department of Morphology, Institute of Biological Science, Federal University of Minas Gerais, MG, Brazil.
Vanessa
V
Pinho
Department of Microbiology, Institute of Biological Science, Federal University of Minas Gerais, MG, Brazil.
Danielle G
DG
Souza
Department of Biochemistry and Immunology, Institute of Biological Science, Federal University of Minas Gerais, MG, Brazil; Postgraduate Program in Health Sciences: Infectious Diseases and Tropical Medicine, Medical School, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Mauro Martins
MM
Teixeira
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
Herbert Bernard
HB
Tanowitz
Department of Biochemistry and Immunology, Institute of Biological Science, Federal University of Minas Gerais, MG, Brazil; Postgraduate Program in Biological Science, NUPEB, Federal University of Ouro Preto, Ouro Preto, MG, Brazil.
Leda Quercia
LQ
Vieira
Department of Biochemistry and Immunology, Institute of Biological Science, Federal University of Minas Gerais, MG, Brazil; Postgraduate Program in Health Sciences: Infectious Diseases and Tropical Medicine, Medical School, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: machadofs@gmail.com.
Fabiana Simão
FS
Machado
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D014355:Chagas Disease / Q000150:complications / Q000276:immunology*; D006790:Host-Parasite Interactions; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009205:Myocarditis / Q000150:complications / Q000276:immunology* / Q000469:parasitology; D009206:Myocardium / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D014349:Trypanosoma cruzi / Q000472:pathogenicity*
D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma
Cytokine; IL-18; Myocarditis; Trypanosoma cruzi