Keratinocyte expression of human beta defensin 2 following bacterial infection: role in cutaneous host defense.
Human beta defensin 2 (hbetaD-2) is thought to play an important role in cutaneous immune defense. We hypothesized that (i) keratinocyte expression of hbetaD-2, measured by reverse transcription-PCR, would be upregulated in response to challenge with pathogenic bacteria, particularly highly adherent strains of Streptococcus pyogenes and Staphylococcus aureus, and (ii) hbetaD-2 would have potent antimicrobial activity against pathogenic but not commensal organisms. Expression of hbetaD-2 was induced consistently by S. aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa, whereas strains of S. pyogenes were poor and variable inducers of hbetaD-2. No correlation was found between levels of bacterial adherence and keratinocyte expression of hbetaD-2. S. pyogenes was significantly more sensitive to killing by hbetaD-2 than S. epidermidis. We conclude that the ability to induce hbetaD-2 expression in combination with sensitivity to its antimicrobial effects may contribute to the rarity of skin infections with the gram-negative bacterial organisms, whereas lack of stimulation of hbetaD-2 expression by S. pyogenes may be important in its ability to evade innate defenses and cause skin disease. Induction of expression of hbetaD-2 but relative tolerance to it may enable S. epidermidis to survive on the skin surface and modulate hbetaD-2 expression when the stratum corneum barrier is disrupted.
Dinulos
James G H
JG
Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington , USA.
Mentele
Laurel
L
Fredericks
L Page
LP
Dale
Beverly A
BA
Darmstadt
Gary L
GL
D001422:Bacterial Adhesion; D001424:Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D012871:Skin Diseases / Q000276:immunology / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000166:cytology / Q000502:physiology; D013297:Streptococcus pyogenes / Q000166:cytology / Q000502:physiology; D015854:Up-Regulation; D023083:beta-Defensins / Q000096:biosynthesis*
C106641:DEFB4A protein, human; D023083:beta-Defensins