The constitutive capacity of human keratinocytes to kill Staphylococcus aureus is dependent on beta-defensin 3.
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 beta-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 beta-defensin 3 in the constitutive killing of bacteria by normal keratinocytes.
Kisich
Kevin O
KO
Division of Pediatric Allergy/Immunology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Howell
Michael D
MD
Boguniewicz
Mark
M
Heizer
Heather R
HR
Watson
Nori U
NU
Leung
Donald Y M
DY
D001706:Biopsy; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013203:Staphylococcal Infections / Q000503:physiopathology / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000254:growth & development / Q000472:pathogenicity*; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
C422950:DEFB103A protein, human; D012333:RNA, Messenger; D023083:beta-Defensins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases