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15 January 2008

Volume 197, Number 2
The Journal of Infectious Diseases 2008;197:214–217
© 2007 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2008/19702-0007$15.00
DOI: 10.1086/524843
BRIEF REPORT

Pharmacologic Augmentation of Hypoxia‐Inducible Factor–1α with Mimosine Boosts the Bactericidal Capacity of Phagocytes

Annelies S. Zinkernagel,1

Carole Peyssonnaux,1,2,a

Randall S. Johnson,1 and

Victor Nizet1,3

1Division of Pediatric Pharmacology and Drug Discovery, School of Medicine, 2Division of Biological Sciences, and 3Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla

Hypoxia‐inducible factor (HIF)–1α is activated on exposure to bacterial pathogens and regulates the innate immune functions of phagocytes. We show here that the HIF‐1α 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.

Received 11 April 2007; accepted 2 August 2007; electronically published 3 January 2008.

Reprints or correspondence: Dr. Victor Nizet, Div. of Pediatric Pharmacology and Drug Discovery, School of Medicine, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Dr., Mail Code 0687, La Jolla, CA 92093‐0687 ().

Cited by

A. M. Timmer, V. Nizet. (2008) IKK /NF- B and the miscreant macrophage. Journal of Experimental Medicine 205:6, 1255-1259
Online publication date: 2-Jul-2008.
CrossRef

  • Potential conflicts of interest: none reported.

    Financial support: National Institutes of Health (grant AI060840 to R.S.J. and V.N.); Swiss National Foundation Fellowship (PBZHB‐108365 to A.S.Z.).

  • Present affiliation: Institut Cochin, Université Paris Descartes, Paris, France.

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