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Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection

Nature Immunology volume 6, pages 57–64 (2005)Cite this article

Abstract

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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Figure 1: Identification of psoriasin as an E. coli–killing protein.
Figure 2: Psoriasin shows antimicrobial activity preferentially against E. coli in various salt and pH conditions.
Figure 3: Psoriasin is focally expressed in human skin and some adnexal structures.
Figure 4: E. coli is effectively killed on human skin and the E. coli–killing activity is inhibited in vivo by a neutralizing antibody to psoriasin.
Figure 5: Psoriasin is secreted in vivo on the body surface.
Figure 6: Bacteria and proinflammatory cytokines induce psoriasin.

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Acknowledgements

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.

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Author notes

  1. Regine Gläser and Jürgen Harder: These authors contributed equally to this work.

Authors and Affiliations

  1. Clinical Research Unit of the Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Germany

    Regine Gläser, Jürgen Harder, Joachim Bartels, Enno Christophers & Jens-Michael Schröder

  2. Institute of Biochemistry, University of Kiel, Germany

    Hans Lange

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  1. Regine Gläser
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Correspondence to Jens-Michael Schröder.

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Supplementary information

Supplementary Fig. 1

Exposure to human skin kills E. coli. (PDF 105 kb)

Supplementary Fig. 2

Purification and isolation of psoriasin. (PDF 285 kb)

Supplementary Fig. 3

Psoriasin bactericidal activity does not cause morphological changes and is not inhibited by Fe2+ and Ca2+. (PDF 284 kb)

Supplementary Fig. 4

The E. coli-killing activity of human skin is inhibited by preincubation with Zn2+ or a neutralizing psoriasin antibody. (PDF 186 kb)

Supplementary Fig. 5

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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