Trypanosoma cruzi-elicited CD8+ T cell-mediated myocarditis: chemokine receptors and adhesion molecules as potential therapeutic targets to control chronic inflammation?
In Chagas disease, during the acute phase, the establishment of inflammatory processes is crucial for Trypanosoma cruzi control in target tissues and for the establishment of host/parasite equilibrium. However, in about 30% of the patients, inflammation becomes progressive, resulting in chronic disease, mainly characterized by myocarditis. Although several hypothesis have been raised to explain the pathogenesis of chagasic myocardiopathy, including the persistence of the parasite and/or participation of autoimmune processes, the molecular mechanisms underlying the establishment of the inflammatory process leading to parasitism control but also contributing to the maintenance of T. cruzi-elicited chronic myocarditis remain unsolved. Trying to shed light on these questions, we have for several years been working with murine models for Chagas disease that reproduce the acute self-resolving meningoencephalitis, the encephalitis resulting of reactivation described in immunodeficient individuals, and several aspects of the acute and chronic myocarditis. In the present review, our results are summarized and discussed under the light of the current literature. Furthermore, rational therapeutic intervention strategies based on integrin-mediated adhesion and chemokine receptor-driven recruitment of leukocytes are proposed to control T. cruzi-elicited unbalanced inflammation.
Lannes-Vieira
Joseli
J
Laboratório de Autoimunidade e Imuno-regulação, Departamento de Imunologia, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil. lannes@ioc.fiocruz.br
D000818:Animals; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002598:Chagas Cardiomyopathy / Q000276:immunology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D006801:Humans; D007111:Immunity, Cellular; D009205:Myocarditis / Q000276:immunology* / Q000517:prevention & control; D019707:Receptors, Chemokine / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
D015815:Cell Adhesion Molecules; D019707:Receptors, Chemokine