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Background  Extracellular vesicles (EVs) are structures with phospholipid bilayer membranes and 100–1000 nm diameters. These vesicles are released from cells upon activation of surface receptors and/or apoptosis. The production of EVs by dendritic cells, mast cells, macrophages, and B and T lymphocytes has been extensively reported in the literature. EVs may express MHC class II and other membrane surface molecules and carry antigens. The aim of this study was to investigate the role of EVs from  Leishmania -infected macrophages as immune modulatory particles.    Methodology/Principal Findings  In this work it was shown that BALB/c mouse bone marrow-derived macrophages, either infected  in vitro  with  Leishmania amazonensis  or left uninfected, release comparable amounts of 50–300 nm-diameter extracellular vesicles (EVs). The EVs were characterized by flow cytometry and electron microscopy. The incubation of naïve macrophages with these EVs for 48 hours led to a statistically significant increase in the production of the cytokines IL-12, IL-1β, and TNF-α.    Conclusions/Significance  EVs derived from macrophages infected with  L. amazonensis  induce other macrophages, which  in vivo  could be bystander cells, to produce the proinflammatory cytokines IL-12, IL-1β and TNF-α. This could contribute both to modulate the immune system in favor of a Th1 immune response and to the elimination of the  Leishmania , leading, therefore, to the control the infection.

Extracellular Vesicles from Leishmania-Infected Macrophages Confer an Anti-infection Cytokine-Production Profile to Naïve Macrophages