PLGA nanoparticles loaded with KMP-11 stimulate innate immunity and induce the killing of Leishmania.

Abstract

UNLABELLED:

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.

• Authors: Diego M Santos, Marcia W Carneiro, Tatiana R de Moura, Manuel Soto, Nívea F Luz, Deboraci B Prates, Juan Manuel Irache, Claudia Brodskyn, Aldina Barral, Manoel Barral-Netto, Socorro Espuelas, Valéria M Borges, Camila I de Oliveira
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 9 Issue 7 Pg. 985-95 (Oct 2013) ISSN: 1549-9642 [Electronic] United States
• PMID: 23603355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Chemokines
• Inflammasomes
• Protozoan Proteins
• Superoxides
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Nitric Oxide
• Lactic Acid
• DNA

Topics

• Animals
• Cell Death (drug effects)
• Chemokines (metabolism)
• DNA (metabolism)
• Female
• Immunity, Innate (drug effects, immunology)
• Inflammasomes (metabolism)
• Lactic Acid (chemistry, pharmacology)
• Leishmania (cytology, drug effects, immunology)
• Macrophage Activation (drug effects, immunology)
• Macrophages (drug effects, metabolism, parasitology, pathology)
• Mice
• Mice, Inbred BALB C
• Nanoparticles (chemistry)
• Nitric Oxide (biosynthesis)
• Polyglycolic Acid (chemistry, pharmacology)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Protozoan Proteins (immunology)
• Superoxides (metabolism)