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Conversely, the immune response induced by<jats:italic>S. mansoni<\/jats:italic>antigens is able to prevent immune-mediated diseases. The aim of this study was to evaluate the potential of the<jats:italic>S. mansoni<\/jats:italic>Sm29 antigen to change the profile of monocyte-derived dendritic cells (MoDCs) from subjects with cutaneous leishmaniasis (CL)<jats:italic>in vitro<\/jats:italic>. Monocytes derived from the peripheral blood mononuclear cells of twelve patients were cultured with GM-CSF and IL-4 for differentiation into dendritic cells and then stimulated with soluble<jats:italic>Leishmania<\/jats:italic>antigen (SLA) in the presence or absence of Sm29 antigen. The expression of surface molecules associated with maturation and activation (HLA-DR, CD40, CD83, CD80, and CD86), inflammation (IL-12, TNF), and downregulation (IL-10, IL-10R) was evaluated using flow cytometry. We observed that the frequencies of HLA-DR, CD83, CD80, and CD86 as well as of IL-10 and IL-10R on MoDCs were higher in cultures stimulated with Sm29, compared to the unstimulated cell cultures. Our results indicate that the Sm29 antigen is able to activate regulatory MoDCs in patients with cutaneous leishmaniasis. 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