1. ¹Department of Dermatology, Heinrich-Heine-University, Duesseldorf, Germany
2. ²Division of Dermatology, Department of Medicine, University of California San Diego and VA San Diego Healthcare System, San Diego, California, USA
3. ³Department of Medical Microbiology, Heinrich-Heine-University, Duesseldorf, Germany
4. ⁴Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
5. ⁵Department of Dermatology, Ludwig-Maximilians-University, Munich, Germany

Correspondence: Amanda S. Büchau, Division of Dermatology, University of California San Diego and VA San Diego Healthcare System, San Diego, California 92307, USA. E-mail: asbuchau@ucsd.edu

⁶Current address: AstraZeneca, Global Clinical Development, Alderley Park, Macclesfield, UK.

Received 20 December 2006; Revised 24 April 2007; Accepted 29 April 2007; Published online 12 July 2007.

Abstract

E. coli is a Gram-negative bacterium rarely found on human skin. We investigated whether direct interaction of E. coli with keratinocytes might induce an innate immune response through recognition by pattern recognition receptors. The capacity of E. coli to activate innate immune responses and IL-8 induction was investigated. We found that E. coli significantly induced human S100A7 and S100A15 transcript abundance and IL-8 release in cultured primary human keratinocytes. S100A15 is a member of the S100 protein family with previously unknown function. E. coli induced effects could be inhibited by neutralizing Toll-like receptor 4 (TLR4) antibodies, suggesting that E. coli-induced IL-8 and S100A15 expression in human keratinocytes are TLR4 dependent. TLR4-/- mice lacked elevated mS100A15 expression after infection with E. coli in contrast to wild-type mice. In vitro, human S100A15 displayed antimicrobial activity against E. coli. Our findings suggest that E. coli modulates S100A15 and IL-8 expression of keratinocytes by recognition through TLR4.