Human healthy skin is continuously exposed to bacteria, but is particularly resistant to the common gut bacterium Escherichia coli. We show here that keratinocytes secrete, as the main E. coli–killing compound, the S100 protein psoriasin in vitro and in vivo in a site-dependent way. In vivo treatment of human skin with antibodies to psoriasin inhibited its E. coli–killing properties. Psoriasin was induced in keratinocytes in vitro and in vivo by E. coli, indicating that its focal expression in skin may derive from local microbial induction. Zn2+-saturated psoriasin showed diminished antimicrobial activity, suggesting that Zn2+ sequestration could be a possible antimicrobial mechanism. Thus, psoriasin may be key to the resistance of skin against E. coli.
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The authors thank H. Janssen, J. Quitzau, M. Brandt, K. Schultz, C. Butzek-Mehrens, A. Preschke, I. Erichsen, R. Rohde, S. Voss and K. Klose (Departments of Dermatology, Medical Microbiology and Otorhinolaryngology, University of Kiel) for technical assistance; D. Blankenburg and H. Pönicke (Department of Dermatology, University of Kiel) for photography; M. Weichenthal (Department of Dermatology, University of Kiel) for statistics; and L. Schwichtenberg, P. Velasco, S. Schubert and H. Lemke (Departments of Dermatology, Medical Microbiology and Biochemistry, University of Kiel) for discussions. Supported by the Deutsche Forschungsgemeinschaft (SFB 617) and in part by the Hensel-Stiftung Kiel.
The authors declare no competing financial interests.
Exposure to human skin kills E. coli. (PDF 105 kb)
Purification and isolation of psoriasin. (PDF 285 kb)
Psoriasin bactericidal activity does not cause morphological changes and is not inhibited by Fe2+ and Ca2+. (PDF 284 kb)
The E. coli-killing activity of human skin is inhibited by preincubation with Zn2+ or a neutralizing psoriasin antibody. (PDF 186 kb)
Skin secretes bioactive psoriasin in vivo. (PDF 84 kb)
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Gläser, R., Harder, J., Lange, H. et al. Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection. Nat Immunol 6, 57–64 (2005). https://doi.org/10.1038/ni1142
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