AvaliaÃÃo do mecanismo de modulaÃÃo da resposta imunolÃgica à Leishmaniose visceral chagasi in vitro em indivÃduos baixos produtores de INF-Y

• Main Author: MÃrcia Sindeaux Frutuoso
• Publication Date: 2009
• Format: Master thesis
• Language: por
• Source: Biblioteca Digital de Teses e Dissertações da UFC
• Download full: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8664
• topic: SLAM; IFN-γ; IL-10; ANATOMIA PATOLOGICA E PATOLOGIA CLINICA

Introduction: Visceral leishmaniasis is a serious public health problem in several parts of the developing world. In leishmaniasis, protection and healing correlate with the development of Th1 immune response, and IFN-γ is considered a key molecule in this response. In contrast, the Th2 response results in disease progression. It is noteworthy that after contact with Leishmania the production of IFN-γ differs between healthy individuals. Some of them are high IFN-γ producer (HIFN-γP), while others respond with low IFN-γ producer (LIFN-γP). This has been observed in the in vitro response to several species of Leishmania, as well as in the early phase of the disease in patients with leishmaniasis. The activation of T lymphocytes can be modulated by immunomodulatory receptors present on the surface of lymphocytes and antigen presenting cells (APCs). Signaling lymphocytic activation molecule (SLAM, CD150) is a transmembrane protein that promotes Th2 differentiation. Evidences support the involvement of this molecule in the immune response against parasites. Objective: To evaluate the role of SLAM signaling pathway in the modulation of immune response of peripheral blood mononuclear cells (PBMC) from individuals low IFN-γ producers (LP) against Leishmania chagasi. Methodology: Healthy individualsâ PBMC were stimulated in vitro with L. chagasi and monoclonal anti-SLAM (α-SLAM), in the presence or not of inflammatory cytokines (rIFN-γ or rIL-12). The supernatants of the cultures were analyzed by ELISA for the determination of IFN-γ and interleukin 10 (IL-10) concentrations. Results: Upon stimulation of PBMC with L. chagasi, the blocking of the SLAM signaling pathway with α-SLAM did not affect the synthesis of IFN-γ and IL-10, regardless of treatment with rIL-12. However, after rIFN-γ treatment of antigen stimulated cells it occurred a download of IL-10 synthesis and upload IFN-γ secretion, regardless of the blockade of SLAM signaling pathway. Conclusions: The blocking of SLAM signaling pathway with α-SLAM at the concentration of 10μg/mL does not interfere significantly in the IFN-γ and IL-10 production of PBMC from individuals LP stimulated with Leishmania chagasi promastigotes. Treatment of PBMC with rIFN-γ is able to induce a reduction of IL-10 and an increment of IFN-γ in the supernates cultures, whereas treatment with rIL-12 enhanced IFN-γ production, but does not interfered with IL-10. It is necessary to make further studies to better understand the role of the SLAM signaling pathway in the immune response of LP against Leishmania chagasi.