Activation of TLR2 by a Small Molecule Produced by Staphylococcus epidermidis Increases Antimicrobial Defense against Bacterial Skin Infections

• Published in: Journal of investigative dermatology Vol. 130; no. 9; pp. 2211 - 2221
• Main Authors: Lai, Yuping, Cogen, Anna L., Radek, Katherine A., Park, Hyun Jeong, MacLeod, Daniel T., Leichtle, Anke, Ryan, Allen F., Di Nardo, Anna, Gallo, Richard L.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2010; Nature Publishing Group; Elsevier Limited
• Subjects: Animals; Antibodies; Antibodies, Neutralizing - immunology; Antimicrobial agents; Antimicrobial peptides; Bacterial Proteins - metabolism; beta-Defensins - genetics; beta-Defensins - metabolism; Biological and medical sciences; Cell culture; Cells, Cultured; Commensals; Culture Media, Conditioned - pharmacology; Defensins; Dermatology; Epidermal Cells; Epidermis - immunology; Epidermis - microbiology; Gene expression; Gene Silencing; Humans; Infection; Keratinocytes; Keratinocytes - cytology; Keratinocytes - microbiology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microorganisms; Pathogens; Signal Transduction - immunology; Skin; Staphylococcal Skin Infections - immunology; Staphylococcal Skin Infections - metabolism; Staphylococcal Skin Infections - prevention & control; Staphylococcus aureus; Staphylococcus epidermidis; Streptococcal Infections - immunology; Streptococcal Infections - metabolism; Streptococcal Infections - prevention & control; Streptococcus; Streptococcus pyogenes; TLR2 protein; Toll-Like Receptor 2 - immunology; Toll-Like Receptor 2 - metabolism; Toll-like receptors; Infection; Staphylococcus epidermidis; Dermatology; Bacteriosis; Bacteria; Micrococcales; Micrococcaceae; Organism defense; Skin; Antimicrobial agent
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2010.123

Production of antimicrobial peptides by epithelia is an essential defense against infectious pathogens. In this study we evaluated whether the commensal microorganism Staphylococcus epidermidis may enhance production of antimicrobial peptides by keratinocytes and thus augment skin defense against infection. Exposure of cultured undifferentiated human keratinocytes to a sterile nontoxic small molecule of <10kDa from S. epidermidis conditioned culture medium (SECM), but not similar preparations from other bacteria, enhanced human β-defensin 2 (hBD2) and hBD3 mRNA expression and increased the capacity of cell lysates to inhibit the growth of group A Streptococcus (GAS) and S. aureus. Partial gene silencing of hBD3 inhibited this antimicrobial action. This effect was relevant in vivo as administration of SECM to mice decreased susceptibility to infection by GAS. Toll-like receptor 2 (TLR2) was important to this process as a TLR2-neutralizing antibody blocked induction of hBDs 2 and 3, and Tlr2-deficient mice did not show induction of mBD4. Taken together, these findings reveal a potential use for normal commensal bacterium S. epidermidis to activate TLR2 signaling and induce antimicrobial peptide expression, thus enabling the skin to mount an enhanced response to pathogens.