title: Staphylococcus aureus Exploits Epidermal Barrier Defects in Atopic Dermatitis to Trigger Cytokine Expression.
abstract: Patients with atopic dermatitis (AD) have an abnormal skin barrier and are frequently colonized by S. aureus. In this study we investigated if S. aureus penetrates the epidermal barrier of subjects with AD and sought to understand the mechanism and functional significance of this entry. S. aureus was observed to be more abundant in the dermis of lesional skin from AD patients. Bacterial entry past the epidermis was observed in cultured human skin equivalents and in mice but was found to be increased in the skin of cathelicidin knockout and ovalbumin-sensitized filaggrin mutant mice. S. aureus penetration through the epidermis was dependent on bacterial viability and protease activity, because killed bacteria and a protease-null mutant strain of S. aureus were unable to penetrate. Entry of S. aureus directly correlated with increased expression of IL-4, IL-13, IL-22, thymic stromal lymphopoietin, and other cytokines associated with AD and with decreased expression of cathelicidin. These data illustrate how abnormalities of the epidermal barrier in AD can alter the balance of S. aureus entry into the dermis and provide an explanation for how such dermal dysbiosis results in increased inflammatory cytokines and exacerbation of disease.
authors.affiliation: Department of Dermatology, University of California-San Diego, California, USA.
authors.forename: Teruaki
authors.initials: T
authors.lastname: Nakatsuji
authors.affiliation: Department of Dermatology, University of California-San Diego, California, USA.
authors.forename: Tiffany H
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Department of Dermatology, University of California-San Diego, California, USA.
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Two
authors.affiliation: Department of Dermatology, University of California-San Diego, California, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Chun
authors.affiliation: Department of Dermatology, University of California-San Diego, California, USA.
authors.forename: Saisindhu
authors.initials: S
authors.lastname: Narala
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Raif S
authors.initials: RS
authors.lastname: Geha
authors.affiliation: Department of Dermatology, University of California-San Diego, California, USA.
authors.forename: Tissa R
authors.initials: TR
authors.lastname: Hata
authors.affiliation: Department of Dermatology, University of California-San Diego, California, USA. Electronic address: rgallo@ucsd.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000235:genetics; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D004817:Epidermis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000091344:Filaggrin Proteins; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000276:immunology / Q000302:isolation & purification*
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D004247:DNA