Poly D,L-lactide-co-glycolide (PLGA) nanoparticle-encapsulated honeybee (Apis melifera) venom promotes clearance of Salmonella enterica serovar Typhimurium infection in experimentally challenged pigs through the up-regulation of T helper type 1 specific immune responses

Vet Immunol Immunopathol. 2014 Oct 15;161(3-4):193-204. doi: 10.1016/j.vetimm.2014.08.010. Epub 2014 Aug 22.

Abstract

Honeybee (Apis melifera) venom (HBV), which includes melittin and lipid-soluble ingredients (chrysin and pinocembrin), elicited increases in the CD4(+)/CD8(+) T lymphocyte ratio, relative mRNA expression levels of the T helper type 1 (Th 1) cytokines (interferon-γ and IL-12) and reinforced viral clearance of an experimental porcine reproductive and respiratory syndrome (PRRS) virus infection in our previous study. On the basis of that previous study, we have now developed poly-d,l-lactide-co-glycolide (PLGA)-encapsulated HBV nanoparticles (P-HBV) for longer sustained release of HBV. We administered P-HBV to pigs via the rectal route, and then evaluated the potential immune-enhancing and bacterial clearance effects of P-HBV against Salmonella enterica serovar Typhimurium. The CD4(+)/CD8(+) lymphocyte ratio, proliferative capacity of peripheral blood lymphocytes and relative mRNA expression levels of IFN-γ and IL-12 (produced mainly by Th1 lymphocytes) were significantly increased in the P-HBV group up to 2 weeks post-administration of P-HBV. After S. Typhimurium infection, the P-HBV group showed a marked reduction in microbial burden in feces and all tissue samples (including the ileum, cecum, colon, and mesenteric lymph node (MLN)), a significant increase in Th 1 cytokines (IFN-γ, IL-2, and IL-12) and a marked decrease in a Th 2 cytokine (IL-4) in all tissue samples and peripheral blood lymphocytes. Thus, P-HBV may be a promising strategy for immune enhancement and prevention of S. Typhimurium or other bacterial infections.

Keywords: Bee venom; Immune enhancing; Melittin; Nanoparticle; PLGA; Salmonella enterica serovar Typhimurium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bee Venoms / chemistry*
  • Lactic Acid*
  • Nanoparticles*
  • Polyglycolic Acid*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Salmonella Infections, Animal / drug therapy*
  • Salmonella typhimurium*
  • Swine
  • Swine Diseases / drug therapy
  • Swine Diseases / microbiology*
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / physiology
  • Up-Regulation

Substances

  • Bee Venoms
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid