Análise da atividade de CD100 na modulação da ativação de macrófagos e sua infectividade por Leishmania (Leishmania) amazonensis.

Abstract

Leishmaniasis is caused by trypanosomatids of the genus Leishmania, which infect mainly macrophages. The disease can have cutaneous, mucocutaneous and visceral forms, and over 350 million people worldwide live at risk areas. The main factors that influence form and severity of the disease are the species of Leishmania and the host immune response. Studies based on infected animal models susceptible and resistant to Leishmania show how the immune system of hosts with different profiles affects the survival of the parasite. Considering the importance of macrophages in Leishmania´s infection and the potential role of CD100 in the modulation of macrophage activation, we postulated that this molecule may affect macrophage infectivity. CD100 is known to reduce migration and expression of inflammatory cytokines in human monocytes and dendritic cells, and is induced in macrophages by inflammatory stimuli. Based on these informations, our objectives are to analyze and compare the expression of CD100 on different types of macrophages from BALB/c and C57BL/6 mice lineages and the effects of this molecule in terms of macrophage activation and infectivity by L. amazonensis. We analyzed the expression of CD100 in resident peritoneal macrophages from both strains of mice and the results suggest that macrophages from BALB/c mice express more CD100 than macrophages from C57BL/6 animals. We have also shown that macrophages from both BALB/c and C57BL/6 mice decrease the expression of CD100 along the infection with Leishmania amazonensis promastigotes. Experiments were also performed to analyze the modulation of soluble CD100 (sCD100) over infection of macrophages from both strains. The results show that macrophages from BALB/c mice pre-treated for 24 hours with sCD100 have augmented infection rates in of 4 hours of incubation. When macrophages remained in contact with the sCD100 before, during and after infection, rates increase after 4 and 24 hours of infection. In macrophages from C57BL/6 mice pre-treated for 24 hours with sCD100 and incubated with sCD100 during the infection rates augment in 4 hours of incubation. When macrophages remained in contact with sCD100 throughout the infection, rates increase after 4 and 24 hours of infection. We can therefore conclude that CD100 is expressed by different macrophage types, that it may be related to modulation of Leishmania´s infection and that the infection itself reduces CD100 expression in macrophages.