Staphylococcus aureus stimulates neutrophil targeting chemokine expression in keratinocytes through an autocrine IL-1alpha signaling loop

J Invest Dermatol. 2010 Jul;130(7):1866-76. doi: 10.1038/jid.2010.37. Epub 2010 Feb 25.


Staphylococcus aureus is a significant human pathogen that can colonize the skin. Neutrophils are well known to be involved in clearance of the bacterium. This study focused on exploring the role that human keratinocytes have as first responders to bacterial challenges. IL-1alpha and IL-1beta increased mRNA production and protein secretion of the neutrophil chemotactic CXCL1, CXCL2, and IL-8 in keratinocytes. S. aureus and the bacterial cell wall components lipoteichoic acid (LTA) and peptidoglycan (PGN) induced similar expression profiles in a Toll-like receptor (TLR)-2-dependent manner. Interestingly, the S. aureus-induced mRNA levels peaked at later time points than those induced by IL-1. The S. aureus-activated chemokine production was preceded by significant IL-1alpha and IL-1beta secretion. Expression of IL-1alpha was significantly higher than that of IL-1beta. Inhibition of IL-1RI using neutralizing antibodies revealed that S. aureus-derived LTA and PGN-induced chemokine expression requires IL-1RI engagement. Surprisingly, we further found that chemokine secretion is dependent upon endocrine IL-1alpha, but not IL-1beta, signaling. Our data show that the innate immune response of keratinocytes is regulated differently than those of other cell types. This may represent a fail-safe system that protects the host against genetic variation and immune evasion mechanisms developed by pathogens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / pharmacology
  • Autocrine Communication / immunology
  • Cell Wall / immunology
  • Cell Wall / metabolism
  • Cells, Cultured
  • Chemokine CXCL1 / genetics
  • Chemokine CXCL1 / metabolism
  • Chemokine CXCL2 / genetics
  • Chemokine CXCL2 / metabolism
  • Chemotaxis, Leukocyte / immunology
  • Humans
  • Interleukin-1alpha / genetics
  • Interleukin-1alpha / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / immunology*
  • Keratinocytes / microbiology
  • Lipopolysaccharides / immunology
  • Neutrophils / cytology
  • Neutrophils / immunology
  • Oligonucleotide Array Sequence Analysis
  • Peptidoglycan / immunology
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-1 / immunology
  • Signal Transduction / immunology*
  • Staphylococcal Skin Infections / immunology*
  • Staphylococcus aureus / immunology*
  • Teichoic Acids / immunology
  • Toll-Like Receptor 2 / metabolism


  • Antibodies, Neutralizing
  • CXCL1 protein, human
  • CXCL2 protein, human
  • Chemokine CXCL1
  • Chemokine CXCL2
  • Interleukin-1alpha
  • Interleukin-1beta
  • Interleukin-8
  • Lipopolysaccharides
  • Peptidoglycan
  • RNA, Messenger
  • Receptors, Interleukin-1
  • TLR2 protein, human
  • Teichoic Acids
  • Toll-Like Receptor 2
  • lipoteichoic acid