Commensal bacteria regulate Toll-like receptor 3-dependent inflammation after skin injury.
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.
Lai
Yuping
Y
[Division of Dermatology, Department of Medicine, University of California-San Diego, San Diego, California, USA.
Di Nardo
Anna
A
Nakatsuji
Teruaki
T
Leichtle
Anke
A
Yang
Yan
Y
Cogen
Anna L
AL
Wu
Zi-Rong
ZR
Hooper
Lora V
LV
Schmidt
Richard R
RR
von Aulock
Sonja
S
Radek
Katherine A
KA
Huang
Chun-Ming
CM
Ryan
Allen F
AF
Gallo
Richard L
RL
D006801:Humans; D007249:Inflammation / Q000382:microbiology*; D017192:Skin Diseases, Bacterial / Q000503:physiopathology*; D013203:Staphylococcal Infections / Q000503:physiopathology*; D051196:Toll-Like Receptor 3 / Q000502:physiology*
D051196:Toll-Like Receptor 3