Nanomedicine: Nanotechnology, Biology and Medicine

Texto completo: acesso restrito. p. 985–995 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-04-29T14:11:17Z No. of bitstreams: 1 1-s2.0-S1549963413001755-main.pdf: 1378587 bytes, checksum: 7f7ed57efe858a0fe0a69d986cc9e5a5 (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2014-09-09T14:49:36Z (GMT) No. of bitstreams: 1 1-s2.0-S1549963413001755-main.pdf: 1378587 bytes, checksum: 7f7ed57efe858a0fe0a69d986cc9e5a5 (MD5) Made available in DSpace on 2014-09-09T14:49:36Z (GMT). No. of bitstreams: 1 1-s2.0-S1549963413001755-main.pdf: 1378587 bytes, checksum: 7f7ed57efe858a0fe0a69d986cc9e5a5 (MD5) Previous issue date: 2013 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.