The outcome of leishmanial infection of macrophages depends on factors particular to each host-parasite combination, involving not only intrinsic properties of the parasite, but also genetically determined characteristics of thehost cell or of its interactions with immunocompetente cells. Human LTA caused by Leishmania (Viannia) braziliensis has a diversity of clinical forms and thehistopathology of the disease is complex. Evaluating the local and systemic immune responses in patients with different clinical presentations may help in defining the role of cells and cytokines in the course of disease. Differentialexpression of cytokines parallels the variation observed on the nature of cellular inflammatory infiltrate, but large variation in the densities of different cell types is usually found among patients, which probably reflects different stages of thedisease. Several immunological mechanisms may account for the tissuedamaging state observed in these patients. In our previous studies, we have shown that the primate Macaca mulatta appears to have significant advantagesover conventional laboratory animals in terms of modeling the human disease, in particular for studying the interactions between parasite and host determinants for infection, disease (virulence) and cure in L. (V.) braziliensis LTA. The goal ofpresent study was to characterize the histological events with time in L. (V.) braziliensis-infected macaques developing self-healing cutaneous lesions. The pathological findings included a typical cell-mediated immunity-inducedgranulomatous reaction (consisting of an aggregation of epitheloid cells and multiple Langhans-type giant cells, surrounded by lymphocytes and plasma cells)that had an effect on the control of parasite replication. Computer-assisted automatic counting of expressed leukocyte immunophenotypes (such as CD20, CD3, CD4, CD8, CD68 and HLA-DR) revealed consistent variation regardingproportions of these cell types. Of note, however, the frequencies of CD4+ were higher than CD8+ T during the evolution of skin lesions. Overall, these findingspoint to the feasibility of using the L. (V.) braziliensis macaque model for further assessing (under more controlled conditions than are possible in clinical studies) the correlates of local and systemic immune responses and the diseaseevolution.
Advisor:Renato Porrozzi de Almeida; Gabriel Grimaldi Filho
School:Faculdades Oswaldo Cruz
Source Type:Master's Thesis
Keywords:Leishmania braziliensis Macaca mulatta
Date of Publication:03/31/2006