Keratinocyte expression of human β 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.