Abstract
BackgroundExtracellular 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 FindingsIn 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/SignificanceEVs 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.
Highlights
Leishmaniases are a disease complex caused by about 21 trypanosomatid protozoa of the genus Leishmania [1,2,3]
IFN-c provides a key stimulus for the development of macrophage resistance to most intracellular pathogens, including the Leishmania [7,8]
The cells differentiated from bone marrow cells were stained with surface antibodies specific for murine monocytes for the purpose of evaluating their phenotype by flow cytometry
Summary
Leishmaniases are a disease complex caused by about 21 trypanosomatid protozoa of the genus Leishmania [1,2,3]. Parasites of that genus have been co-evolving with their mammals and insect hosts for thousands of years. It is not surprising, that they are well adapted to these hosts and vectors, persisting and replicating in their tissues, subverting the immune response of the vertebrate host, and spreading to other hosts of the same or of another species. 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. The aim of this study was to investigate the role of EVs from Leishmania-infected macrophages as immune modulatory particles
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