Recombinant murine IL-12 promotes a protective Th1/cellular response in Mongolian gerbils infected with Sporothrix schenckii

J Chemother. 2015 Feb;27(2):87-93. doi: 10.1179/1973947814Y.0000000174. Epub 2014 Feb 18.

Abstract

Sporotrichosis is a cutaneous fungal infection caused by Sporothrix schenckii. It is known to be mainly contained by Th1 responses. As IL-12 is crucial for Th1 response, we investigated if treatment with recombinant murine IL-12 (rmIL-12) promoted Th1 immunity and/or clinical improvement in an experimental sporotrichosis gerbil model. Gerbils were inoculated with S. schenckii in the footpad and treated with rmIL-12. Seven days post infection there was a significant increase in macrophage phagocytosis and oxidative burst, and in delayed-type hypersensitivity (DTH) reaction in rmIL-12 treated gerbils, as well as a ∼10-fold increase of serum IFN-gamma and a decrease of IL-4 and IL-10. Moreover, rmIL-12 substantially decreased (∼70%) S. schenckii burden in liver and spleen and improved the clinical outcome preventing footpad ulcer and tail nodules observed in untreated gerbils. Our study demonstrates that rmIL-12 promotes Th1 immune response against S. schenckii favouring its clearance and preventing clinical symptoms.

Keywords: IL-12,; Meriones unguiculatus,; Sporothrix schenckii,; Sporotrichosis,; Th1 response.

MeSH terms

  • Animals
  • Antifungal Agents / metabolism
  • Antifungal Agents / therapeutic use
  • Cells, Cultured
  • Coculture Techniques
  • Drug Hypersensitivity / immunology
  • Drug Hypersensitivity / microbiology
  • Drug Hypersensitivity / pathology
  • Drug Hypersensitivity / prevention & control
  • Gerbillinae
  • Immunity, Cellular / drug effects
  • Immunity, Innate / drug effects*
  • Immunologic Factors / genetics
  • Immunologic Factors / metabolism
  • Immunologic Factors / therapeutic use*
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism
  • Interleukin-12 / therapeutic use*
  • Liver / drug effects
  • Liver / immunology
  • Liver / microbiology
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / microbiology
  • Macrophages, Peritoneal / pathology
  • Male
  • Mice
  • Phagocytosis / drug effects
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / therapeutic use
  • Respiratory Burst / drug effects
  • Specific Pathogen-Free Organisms
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / microbiology
  • Sporothrix / drug effects
  • Sporothrix / immunology*
  • Sporothrix / isolation & purification
  • Sporotrichosis / drug therapy*
  • Sporotrichosis / immunology
  • Sporotrichosis / microbiology
  • Sporotrichosis / pathology
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th1 Cells / microbiology

Substances

  • Antifungal Agents
  • Immunologic Factors
  • Recombinant Proteins
  • Interleukin-12