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Distribution of inflammatory cells and cytokine-producing cells in cardiac muscle of Calomys callosus infected with Trypanosma cruzi in the acute and chronic phase of infection and after immunosuppression

Grant number: 11/10147-3
Support type:Regular Research Grants
Duration: December 01, 2011 - November 30, 2013
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Noemi Nosomi Taniwaki
Grantee:Noemi Nosomi Taniwaki
Home Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Since initial works of Carlos Chagas (1909), many studies have been developed in different vertebrates to gather information about the evolutive process of Trypanosoma cruzi infection and the mechanisms involved on the pathogenesis of the Chagas' disease, however, many aspectsare still unknown. The development of chronic, active and fibrosing myocarditis after a prolonged asymptomatic infection is still a controvertial subject and sofar, it has not been elucidated in the pathogenesis of chronic Chagas' disease. Some studies suggest an autoimmune hypothesis for the chronic disease, in which the symptoms presented by infected individuals are a consequence of triggered immune responses against self antigens. However, autoimmunity is not sufficient to explain the multifocal nature of myocarditis and the preferential location of fibrosis in certain heart regions. Moreover, frequent positive xenodiagnosis during the chronicphase of the disease and episodes of reactivation in immuno compromised patients has provided evidence that parasite is present even under active control of the host immunological system. Recent studies have described apositive correlation between myocardial parasite persistence and the highgrade myocarditis. These studies reinforce the notion that a combination of immune response and parasite persistence determines the development of Chagas' disease. However, the specific mechanisms that trigger thesymptoms observed during the chronic phase are still elusive. Calomys callosus, a sylvatic rodent represent a peculiar experimental model in the study of development of Chagas' disease. This animal has the capacity to control the infection with different strains of T. cruzi, including those considerated the most virulent strain of T. cruzi. Studies have demonstrated that Calomys are capable to revert spontaneously tissue lesions and fibrosis, without specific treatment, independently of the type of involved collagen. Calomys is also capable to survive thereactivation with high grade of parasitemia and myocarditis. It has been suggested that the use of different mouse, experimental modeland parasite strains might explain the discrepancy concerning the identity of inflammatory cells in T. cruzi infection in the acute and chronicphase. Inflammatory cells associated with a concomitant cytokine producing cells might be involved in the response to T. cruzi infection. Generally, the absence of some components of the immune response leads to greater susceptibility to T. cruzi infection, resulting in higher parasitemia and mortality rates. The determination of the role of the immune response in Chagas' disease development is more difficult due to the fact that relatively little is known about the immunological characteristics of the site of disease inchronic T. cruzi infection. A study of the local immune responses inchagasic heart lesions might provide insight into the pathogenesis of Chagas' disease and the regulation of host resistance to the infection. In this study, we propose to develop an experimental model in Calomy callosus to gather information about the development of Chagas' disease in different stages of infection. Calomys will be infected with G (T.cruzi I), Y (T. cruzi II) and CL (T. cruzi VI) strains of T. cruzi. Immunofluorescence will be carried out in order to examine the distribution of inflammatory cells (CD4, CD8, Mac, CD20, Neutrophil, NKcells) and cytokine producing cells (IFN ³, TGF ², TNF ±) in the myocardium of Calomys infected with T. cruzi in the acute, chronic and immunosuppressed animals. (AU)