Skin commensals amplify the innate immune response to pathogens by activation of distinct signaling pathways.
Little is known about the impact of different microbial signals on skin barrier organ function and the interdependency between resident microflora and pathogenic microorganisms. This study shows that commensal and pathogenic staphylococci differ in their ability to induce expression of antimicrobial peptides/proteins (AMPs) and activate different signaling pathways in human primary keratinocytes. Whereas secreted factors of skin commensals induce expression of the AMPs HBD-3 and RNase7 in primary human keratinocytes via Toll-like receptor (TLR)-2, EGFR, and NF-κB activation, those of pathogenic staphylococci activate the mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT signaling pathways and suppress NF-κB activation. Interestingly, commensal bacteria are able to amplify the innate immune response of human keratinocytes to pathogens by increased induction of AMP expression and abrogation of NF-κB suppression, suggesting that the two activation pathways can act in a synergistic way. These data indicate that commensal and pathogenic microorganisms evolved specific mechanisms to modulate innate immunity of the skin.
Department of Dermatology, Eberhard-Karls-University Tübingen, Tübingen, Germany.
Ines
I
Wanke
Heiko
H
Steffen
Christina
C
Christ
Bernhard
B
Krismer
Friedrich
F
Götz
Andreas
A
Peschel
Martin
M
Schaller
Birgit
B
Schittek
D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D013212:Staphylococcus epidermidis / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D023083:beta-Defensins / Q000378:metabolism
C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D016328:NF-kappa B; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D023083:beta-Defensins; D066246:ErbB Receptors; D012260:Ribonucleases; C470000:Ribonuclease 7