CCR5 plays a critical role in the development of myocarditis and host protection in mice infected with Trypanosoma cruzi.
The pathogenesis of myocarditis during Trypanosoma cruzi infection is poorly understood. We investigated the role played by chemokine receptor 5 (CCR5) in the influx of T cells to the cardiac tissue of T. cruzi-infected mice. mRNA and protein for the CCR5 ligands CCL3, CCL4, and CCL5 were detected in the hearts of infected mice in association with CD4+ and CD8+ T cells. There was a high level of CCR5 expression on CD8+ T cells in the hearts of infected mice. Moreover, CCR5 expression on CD8+ T cells was positively modulated by T. cruzi infection. CCR5-deficient mice infected with T. cruzi experienced a dramatically inhibited migration of T cells to the heart and were also more susceptible to infection. These results suggest that CCR5 and its ligands play a central role in the control of T cell influx in T. cruzi-infected mice. Knowledge of the mechanisms that trigger and control the migration of cells to the heart in patients with Chagas disease may help in the design of drugs that prevent myocarditis and protect against the development of severe disease.
Machado
Fabiana S
FS
Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Koyama
Natalia S
NS
Carregaro
Vanessa
V
Ferreira
Beatriz R
BR
Milanezi
Cristiane M
CM
Teixeira
Mauro M
MM
Rossi
Marcos A
MA
Silva
João S
JS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D019713:Receptors, CCR5 / Q000032:analysis / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
C496534:Ccl3 protein, mouse; C496535:Ccl4 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019713:Receptors, CCR5