Commensal bacteria regulate toll-like receptor 3-dependent inflammation after skin injury

Yuping Lai, Anna Di Nardo, Teruaki Nakatsuji, Anke Leichtle, Yan Yang, Anna L. Cogen, Zi Rong Wu, Lora V. Hooper, Richard R. Schmidt, Sonja Von Aulock, Katherine A. Radek, Chun Ming Huang, Allen F. Ryan, Richard L. Gallo

Research output: Contribution to journalArticle

356 Citations (Scopus)

Abstract

The normal microflora of the skin includes staphylococcal species that will induce inflammation when present below the dermis but are tolerated on the epidermal surface without initiating inflammation. Here we reveal a previously unknown mechanism by which a product of staphylococci inhibits skin inflammation. This inhibition is mediated by staphylococcal lipoteichoic acid (LTA) and acts selectively on keratinocytes triggered through Toll-like receptor 3(TLR3). We show that TLR3 activation is required for normal inflammation after injury and that keratinocytes require TLR3 to respond to RNA from damaged cells with the release of inflammatory cytokines. Staphylococcal LTA inhibits both inflammatory cytokine release from keratinocytes and inflammation triggered by injury through a TLR2-dependent mechanism. To our knowledge, these findings show for the first time that the skin epithelium requires TLR3 for normal inflammation after wounding and that the microflora can modulate specific cutaneous inflammatory responses.

Original languageEnglish (US)
Pages (from-to)1377-1382
Number of pages6
JournalNature Medicine
Volume15
Issue number12
DOIs
StatePublished - Dec 2009

Fingerprint

Toll-Like Receptor 3
Bacteria
Skin
Inflammation
Wounds and Injuries
Keratinocytes
Cytokines
Chemical activation
RNA
Dermis
Staphylococcus
Epithelium

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lai, Y., Di Nardo, A., Nakatsuji, T., Leichtle, A., Yang, Y., Cogen, A. L., ... Gallo, R. L. (2009). Commensal bacteria regulate toll-like receptor 3-dependent inflammation after skin injury. Nature Medicine, 15(12), 1377-1382. https://doi.org/10.1038/nm.2062

Commensal bacteria regulate toll-like receptor 3-dependent inflammation after skin injury. / Lai, Yuping; Di Nardo, Anna; Nakatsuji, Teruaki; Leichtle, Anke; Yang, Yan; Cogen, Anna L.; Wu, Zi Rong; Hooper, Lora V.; Schmidt, Richard R.; Von Aulock, Sonja; Radek, Katherine A.; Huang, Chun Ming; Ryan, Allen F.; Gallo, Richard L.

In: Nature Medicine, Vol. 15, No. 12, 12.2009, p. 1377-1382.

Research output: Contribution to journalArticle

Lai, Y, Di Nardo, A, Nakatsuji, T, Leichtle, A, Yang, Y, Cogen, AL, Wu, ZR, Hooper, LV, Schmidt, RR, Von Aulock, S, Radek, KA, Huang, CM, Ryan, AF & Gallo, RL 2009, 'Commensal bacteria regulate toll-like receptor 3-dependent inflammation after skin injury', Nature Medicine, vol. 15, no. 12, pp. 1377-1382. https://doi.org/10.1038/nm.2062
Lai Y, Di Nardo A, Nakatsuji T, Leichtle A, Yang Y, Cogen AL et al. Commensal bacteria regulate toll-like receptor 3-dependent inflammation after skin injury. Nature Medicine. 2009 Dec;15(12):1377-1382. https://doi.org/10.1038/nm.2062
Lai, Yuping ; Di Nardo, Anna ; Nakatsuji, Teruaki ; Leichtle, Anke ; Yang, Yan ; Cogen, Anna L. ; Wu, Zi Rong ; Hooper, Lora V. ; Schmidt, Richard R. ; Von Aulock, Sonja ; Radek, Katherine A. ; Huang, Chun Ming ; Ryan, Allen F. ; Gallo, Richard L. / Commensal bacteria regulate toll-like receptor 3-dependent inflammation after skin injury. In: Nature Medicine. 2009 ; Vol. 15, No. 12. pp. 1377-1382.
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