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Activation of TLR2 by a Small Molecule Produced by Staphylococcus epidermidis Increases Antimicrobial Defense against Bacterial Skin Infections
Open accessAbstract
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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“Commensal organisms such as strains of Staphylococcus epidermidis found in the skin secrete compounds that are themselves antibacterial, such as phenol-soluble modulins,4,5 and also interact with the host to induce AMP expression6 or reduce inflammation.6”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [6]
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“In fact, recent mouse studies further revealed that murine β-defensin 3 (the ortholog of hBD2) and Reg3γ (ortholog of REG3A), but not S100A8, have wound healing-promoting properties as they could rescue defective wound healing in IL-17A−/− mice, which show defective AMP induction.6,30”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [6]
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“Bacterial colonization does not necessarily cause inflammation,6,19,20 but high endotoxin levels and other microbial products can drive inflammatory responses.”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [6]
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Metadata
- 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
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 130
- Issue
- 9
- Pages
- 2211-2221
- ISSN
- 0022-202X (ISSN-L)
- 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
- 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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