Cited by 447Antimicrobial Peptides and ActivitiesImmune Response and InflammationDermatology and Skin Diseases

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

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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.·2010·Journal of Investigative Dermatology

DOI 10.1038/jid.2010.123PMC PMC2922455

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Abstract

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 <10 kDa from S. epidermidis conditioned culture medium (SECM), but not similar preparations from other bacteria, enhanced human beta-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.

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Authors: Lai, Y., Cogen, A. L., Radek, K. A., Park, H. J., MacLeod, D. T., Leichtle, A., Ryan, A. F., Di Nardo, A., & Gallo, R. L.
Affiliations: University of California San Diego (US)
Corresponding author: Gallo, Richard L.
ORCID: Lai, Yuping
Cogen, Anna L.
Park, Hyun Jeong
MacLeod, Daniel T.
Leichtle, Anke
Ryan, Allen F.
Gallo, Richard L.
Venue: Journal of Investigative Dermatology
Publisher: Elsevier BV
Published: 2010-09
Volume: 130
Issue: 9
Pages: 2211-2221
ISSN: 0022-202X (ISSN-L)
DOI: 10.1038/jid.2010.123
PMC: PMC2922455
OpenAlex: W2117733468
Cited by: 446
References: 60
Citations by year: 2026: 22 · 2025: 41 · 2024: 22 · 2023: 26 · 2022: 37 · 2021: 36 · 2020: 30 · 2019: 32 · 2018: 33 · 2017: 29 · 2016: 32 · 2015: 21 · 2014: 27 · 2013: 24 · 2012: 13
FWCI: 16.49
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1918 d)
Locations: Journal of Investigative Dermatology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
Funders: National Institutes of Health (R01-AI052453)
National Institute on Alcohol Abuse and Alcoholism (P30AA019373)
National Institute on Deafness and Other Communication Disorders (DC006279, R01DC006279)
National Institute of Allergy and Infectious Diseases (R01AI052453, R56AI083358, R01AI083358, R37AI052453)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR052728)
Topics: Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Keywords: Staphylococcus epidermidis, TLR2, antimicrobial peptides, human beta-defensin 2, human beta-defensin 3, keratinocytes, skin infections, commensal bacteria, Streptococcus pyogenes, Staphylococcus aureus, innate immunity, bacterial skin infections
MeSH terms: Epidermal Cells, Animals, Bacterial Proteins, Cells, Cultured, Epidermis, Humans, Mice, Inbred C57BL, Staphylococcal Skin Infections, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcal Infections, Streptococcus pyogenes, Signal Transduction, Keratinocytes, Culture Media, Conditioned, Mice, Knockout, Gene Silencing, beta-Defensins, Toll-Like Receptor 2, Mice, Antibodies, Neutralizing

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

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