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