Pharmacologic augmentation of hypoxia-inducible factor-1alpha with mimosine boosts the bactericidal capacity of phagocytes |
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Authors: | Zinkernagel Annelies S Peyssonnaux Carole Johnson Randall S Nizet Victor |
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Affiliation: | 1Division of Pediatric Pharmacology and Drug Discovery, School of Medicine, University of California, San Diego, La Jolla 92093-0687, USA. |
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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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