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      Pharmacologic augmentation of hypoxia-inducible factor-1alpha with mimosine boosts the bactericidal capacity of phagocytes.

      The Journal of Infectious Diseases
      Animals, Blood Bactericidal Activity, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, agonists, immunology, Immunity, Innate, Mice, Mice, Inbred C57BL, Mimosine, pharmacology, Monocytes, Neutrophils, Phagocytes, Respiratory Burst, Staphylococcal Infections, drug therapy, microbiology, Staphylococcal Skin Infections, Staphylococcus aureus, drug effects, pathogenicity, U937 Cells

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          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.

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