The Constitutive Capacity of Human Keratinocytes to Kill Staphylococcus aureus Is Dependent on β-Defensin 3

Kisich, Kevin O.; Howell, Michael D.; Boguniewicz, Mark; Heizer, Heather R.; Watson, Nori U.; Leung, Donald Y. M.
October 2007
Journal of Investigative Dermatology;Oct2007, Vol. 127 Issue 10, p2368
Academic Journal
Normal skin is often exposed to bacteria, including potent pathogens such as E. coli, Staphylococcus aureus, and Streptococcus sp., but these microbes usually do not cause skin inflammation or infection in healthy individuals. Therefore, we hypothesized that there must be a constitutive mechanism for rapid destruction and elimination of small numbers of bacteria which penetrate the stratum corneum from everyday activities. This study found that exposure of keratinocytes cultured from a number of individuals to S. aureus resulted in approximately 2–3 log better killing than by HaCaT cells within 1 hour. Killing required contact between the keratinocytes and the bacteria, but was not dependent on internalization. Contact between the bacteria and the keratinocytes resulted in rapid deposition of several antimicrobial peptides onto the bacteria, but only human β-defensin (HBD) 3 accumulated at levels sufficient to account for killing when S. aureus were exposed to human skin explants. Blocking peptide binding of HBD3 inhibited killing of the bacteria, indicating an essential role for β-defensin 3 in the constitutive killing of bacteria by normal keratinocytes.Journal of Investigative Dermatology (2007) 127, 2368–2380; doi:10.1038/sj.jid.5700861; published online 26 April 2007


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