Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human β-defensin-3

• Published in: Journal of allergy and clinical immunology Vol. 122; no. 1; pp. 62 - 68
• Main Authors: Kisich, Kevin O., Carspecken, Charles W., Fiéve, Stephanie, Boguniewicz, Mark, Leung, Donald Y.M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2008; Elsevier
• Subjects: Allergic diseases; Allergy and Immunology; Antimicrobial peptides; bacterial infections; beta-Defensins - immunology; beta-Defensins - metabolism; Biological and medical sciences; Cells, Cultured; defensins; Dermatitis, Atopic - immunology; Dermatitis, Atopic - microbiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; human; Humans; Immunopathology; Interleukin-13 - immunology; Interleukin-13 - metabolism; Interleukin-4 - immunology; Interleukin-4 - metabolism; keratinocytes; Keratinocytes - cytology; Keratinocytes - immunology; Keratinocytes - metabolism; Medical sciences; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; skin; Skin allergic diseases. Stinging insect allergies; Staphylococcal Skin Infections - immunology; Staphylococcal Skin Infections - microbiology; Staphylococcus aureus - immunology; Th2 Cells - immunology; Th2 Cells - metabolism; KGM; defensins; AD; HBD-3; Antimicrobial peptides; MRSA; skin; DAPI; keratinocytes; bacterial infections; human; Keratinocyte Growth Medium; 4′-6-Diamidino-2-phenylindole, dihydrochloride; Human β-defensin-3; Atopic dermatitis; Methicillin-resistant Staphylococcus aureus; Allergy; Skin disease; Peptides; Antimicrobial agent; Atopy; Association; Immunology; Bacteria; Micrococcales; Keratinocyte; Micrococcaceae; Staphylococcus aureus; Human; Immunopathology; Deficiency; Infection; Mobilization; Bacteriosis; Skin; Defensin
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2008.04.022

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 β-defensin-3 (HBD-3). 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. 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 TH2 cytokines on the ability of the cells to synthesize and mobilize HBD-3, and to kill S aureus. 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. Patients with AD have problems with S aureus skin infection. This is a result of increased levels of TH2 cytokines, which inhibit keratinocyte mobilization of HBD-3.