title: PLGA nanoparticles loaded with KMP-11 stimulate innate immunity and induce the killing of Leishmania.
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.
  
  
  BACKGROUND
  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.affiliation: Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brazil.
authors.forename: Diego M
authors.initials: DM
authors.lastname: Santos
authors.forename: Marcia W
authors.initials: MW
authors.lastname: Carneiro
authors.forename: Tatiana R
authors.initials: TR
authors.lastname: de Moura
authors.forename: Manuel
authors.initials: M
authors.lastname: Soto
authors.forename: Nívea F
authors.initials: NF
authors.lastname: Luz
authors.forename: Deboraci B
authors.initials: DB
authors.lastname: Prates
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Irache
authors.forename: Claudia
authors.initials: C
authors.lastname: Brodskyn
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
authors.forename: Socorro
authors.initials: S
authors.lastname: Espuelas
authors.forename: Valéria M
authors.initials: VM
authors.lastname: Borges
authors.forename: Camila I
authors.initials: CI
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D058847:Inflammasomes / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry* / Q000494:pharmacology; D007891:Leishmania / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000096:biosynthesis; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015800:Protozoan Proteins / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D018925:Chemokines; D058847:Inflammasomes; D015800:Protozoan Proteins; D013481:Superoxides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D009569:Nitric Oxide; D019344:Lactic Acid; D004247:DNA
keywords: Innate response; Leishmania; Macrophage; Nanoparticle; PLGA