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

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.

Leishmania infantum Modulates Host Macrophage Mitochondrial Metabolism by Hijacking the SIRT1-AMPK Axis

“…Pkm2 transcription has been related with macrophage [20,21] and NF-kB activation [22]. This phenomenon suggests that bystander macrophages could be activated in a similar fashion as it was demonstrated to occur with bystander dendritic cells [23,24] or even by infected macrophage secreted extracellular vesicles [25]. From the early energetic and metabolic settings responsible for a glycolytic environment resulted a nutrient and energetic deficit.…”

Dynamic flux of microvesicles modulate parasite-host cell interaction ofTrypanosoma cruziin eukaryotic cells

“…The ability of protozoan parasites to release EVs has also been reported in Leishmania spp. (Silverman et al, , ; Cronemberger‐Andrade et al, ; Hassani, Shio, Martel, Faubert, & Olivier, ), T. vaginalis (Twu et al, ), Giardia (Deolindo, Evans‐Osses, & Ramirez, ), T. brucei (Geiger et al, ), T. gondii (Pope and Lesser, ), Plasmodium spp. (Campos et al, ; Couper et al, ; Martin‐Jaular, Nakayasu, Ferrer, Almeida, & Del Portillo, ; Nantakomol et al, ; Mantel et al, ; Regev‐Rudzki et al, ).…”

Extracellular vesicles as mediators of immunopathology in infectious diseases

“…Leishmania ‐infected macrophages produce various EV which can enhance the production of the proinflammatory cytokines TNF, IL‐1β and IL‐12 by naïve macrophages. This can contribute to a stimulation of immune responses favoring a shift toward Th1 responses as well as eliminating Leishmania to control infection …”