Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human beta-defensin-3.
BACKGROUND
Individuals with atopic dermatitis (AD) have frequent colonization and infection with Staphylococcus aureus. Rapid elimination of S. aureus depends on constitutive synthesis and mobilization of human beta-defensin-3 (HBD-3).


OBJECTIVE
To determine whether keratinocytes in AD, compared with normal, skin are less able to kill S. aureus rapidly, and to assess the potential role that abnormally low mobilization of HBD-3 onto S. aureus has in this process.


METHODS
Skin samples from 10 normal individuals and 10 patients with AD were compared for synthesis and mobilization of HBD-3 onto surface-associated S. aureus. Furthermore, keratinocytes from 10 individuals were studied for the effects of T(H)2 cytokines on the ability of the cells to synthesize and mobilize HBD-3, and to kill S. aureus.


RESULTS
Keratinocytes in skin biopsies from subjects with AD were defective in killing S. aureus relative to normal individuals (P < .001). The constitutive levels of HBD-3 in the epidermal keratinocytes were similar between normal individuals and those with AD. However, the cells of patients with AD were unable to mobilize HBD-3 efficiently to kill S. aureus. Physiologic Ca(++) was essential for development of normal HBD-3 levels by cultured human keratinocytes. Mobilization of HBD-3 and the ability to kill S. aureus were significantly (P < .05) inhibited by IL-4 and IL-13. Antagonism of IL-4/10/13 with antibodies significantly (P < .01) improved mobilization of HBD-3 onto the surface of S. aureus by skin from patients with AD.


CONCLUSIONS
Patients with AD have problems with S. aureus skin infection. This is a result of increased levels of T(H)2 cytokines, which inhibit keratinocyte mobilization of HBD-3.
Division of Allergy/Immunology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colo 80206, USA.
Kevin O
KO
Kisich
Charles W
CW
Carspecken
Stephanie
S
Fiéve
Mark
M
Boguniewicz
Donald Y M
DY
Leung
D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013207:Staphylococcal Skin Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D023083:beta-Defensins / Q000276:immunology / Q000378:metabolism*
C422950:DEFB103A protein, human; D018793:Interleukin-13; D023083:beta-Defensins; D015847:Interleukin-4