1. PLGA nanoparticles loaded with KMP-11 stimulate innate immunity and induce the killing of Leishmania.
- Author
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Santos DM, Carneiro MW, de Moura TR, Soto M, Luz NF, Prates DB, Irache JM, Brodskyn C, Barral A, Barral-Netto M, Espuelas S, Borges VM, and de Oliveira CI
- Subjects
- Animals, Cell Death drug effects, Chemokines metabolism, DNA metabolism, Female, Immunity, Innate drug effects, Inflammasomes metabolism, Lactic Acid pharmacology, Leishmania drug effects, Macrophage Activation drug effects, Macrophage Activation immunology, Macrophages drug effects, Macrophages metabolism, Macrophages parasitology, Macrophages pathology, Mice, Mice, Inbred BALB C, Nitric Oxide biosynthesis, Polyglycolic Acid pharmacology, Polylactic Acid-Polyglycolic Acid Copolymer, Superoxides metabolism, Immunity, Innate immunology, Lactic Acid chemistry, Leishmania cytology, Leishmania immunology, Nanoparticles chemistry, Polyglycolic Acid chemistry, Protozoan Proteins immunology
- Abstract
We recently demonstrated that immunization with polyester poly(lactide-co-glycolide acid) (PLGA) nanoparticles loaded with the 11-kDa Leishmania vaccine candidate kinetoplastid membrane protein 11 (KMP-11) significantly reduced parasite load in vivo. Presently, we explored the ability of the recombinant PLGA nanoparticles to stimulate innate responses in macrophages and the outcome of infection with Leishmania braziliensis in vitro. Incubation of macrophages with KMP-11-loaded PLGA nanoparticles significantly decreased parasite load. In parallel, we observed the augmented production of nitric oxide, superoxide, TNF-α and IL-6. An increased release of CCL2/MCP-1 and CXCL1/KC was also observed, resulting in macrophage and neutrophil recruitment in vitro. Lastly, the incubation of macrophages with KMP-11-loaded PLGA nanoparticles triggered the activation of caspase-1 and the secretion of IL-1β and IL-18, suggesting inflammasome participation. Inhibition of caspase-1 significantly increased the parasite load. We conclude that KMP-11-loaded PLGA nanoparticles promote the killing of intracellular Leishmania parasites through the induction of potent innate responses., From the Clinical Editor: In this novel study, KMP-11-loaded PLGA nanoparticles are demonstrated to promote the killing of intracellular Leishmania parasites through enhanced innate immune responses by multiple mechanisms. Future clinical applications would have a major effect on our efforts to address parasitic infections., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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