Abstract
Hypoxia-inducible factor (HIF)-1alpha is activated on exposure to bacterial pathogens and regulates the innate immune functions of phagocytes. We show here that the HIF-1alpha agonist mimosine can boost the capacity of human phagocytes and whole blood to kill the leading pathogen Staphylococcus aureus in a dose-dependent fashion and reduce the lesion size in a murine model of S. aureus skin infection. This provides the first proof of principle for a novel approach to the treatment of bacterial infection by pharmacologically augmenting the host phagocytic function.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Bactericidal Activity
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / agonists*
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Hypoxia-Inducible Factor 1, alpha Subunit / immunology*
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Immunity, Innate
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Mice
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Mice, Inbred C57BL
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Mimosine / pharmacology*
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Monocytes / immunology
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Neutrophils / immunology
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Phagocytes / immunology
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Respiratory Burst
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Staphylococcal Infections / drug therapy
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Staphylococcal Infections / immunology
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Staphylococcal Infections / microbiology
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Staphylococcal Skin Infections / drug therapy*
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Staphylococcal Skin Infections / immunology*
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Staphylococcal Skin Infections / microbiology
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Staphylococcus aureus / drug effects*
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Staphylococcus aureus / pathogenicity
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U937 Cells
Substances
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Hypoxia-Inducible Factor 1, alpha Subunit
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Mimosine