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Keratinocyte Expression Of Human β Defensin 2 Following Bacterial Infection: Role In Cutaneous Host Defense

James G. H. Dinulos, Laurel Mentele, L. Page Fredericks, Beverly A. Dale, Gary L. Darmstadt

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ABSTRACT Human β defensin 2 (hβD-2) is thought to play an important role in cutaneous immune defense. We hypothesized that (i) keratinocyte expression of hβD-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) hβD-2 would have potent antimicrobial activity against pathogenic but not commensal organisms. Expression of hβD-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 hβD-2. No correlation was found between levels of bacterial adherence and keratinocyte expression of hβD-2. S . pyogenes was significantly more sensitive to killing by hβD-2 than S . epidermidis . We conclude that the ability to induce hβD-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 hβD-2 expression by S . pyogenes may be important in its ability to evade innate defenses and cause skin disease. Induction of expression of hβD-2 but relative tolerance to it may enable S . epidermidis to survive on the skin surface and modulate hβD-2 expression when the stratum corneum barrier is disrupted.