title: Staphylococcus aureus penetrate the interkeratinocyte spaces created by skin-infiltrating neutrophils in a mouse model of impetigo.
abstract: BACKGROUND
  Impetigo is a bacterial skin disease characterized by intraepidermal neutrophilic pustules. Previous studies have demonstrated that exfoliative toxin producing staphylococci are isolated in the cutaneous lesions of human and canine impetigo. However, the mechanisms of intraepidermal splitting in impetigo remain poorly understood.
  
  
  OBJECTIVE
  To determine how staphylococci penetrate the living epidermis and create intraepidermal pustules in vivo using a mouse model of impetigo.
  
  
  METHODS
  Three Staphylococcus aureus strains harbouring the etb gene and three et gene negative strains were epicutaneously inoculated onto tape-stripped mouse skin. The skin samples were subjected to time course histopathological and immunofluorescence analyses to detect intraepidermal neutrophils and infiltrating staphylococci. To determine the role of neutrophils on intraepidermal bacterial invasion, cyclophosphamide (CPA) was injected intraperitoneally into the mice to cause leucopenia before the inoculation of etb gene positive strains.
  
  
  RESULTS
  In mice inoculated with etb gene positive S. aureus, intraepidermal pustules resembling impetigo were detected as early as 4 h post-inoculation (hpi). Neutrophils in the epidermis were detected from 4 hpi, whereas intraepidermal staphylococci was detected from 6 hpi. The dimensions of the intraepidermal clefts created in mice inoculated with etb gene positive strains at 6 hpi were significantly larger than those in mice inoculated with et gene negative strains. In CPA treated mice, staphylococci or neutrophils were not detected in the deep epidermis until 6 hpi.
  
  
  CONCLUSIONS
  Our findings indicate that intraepidermal neutrophils play an important role in S. aureus invasion into the living epidermis in a mouse model of impetigo.
authors.affiliation: Laboratory of Veterinary Internal Medicine, Division of Animal Life Science, Graduate School, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo, 183-8509, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Imanishi
authors.affiliation: Laboratory of Veterinary Internal Medicine, Division of Animal Life Science, Graduate School, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo, 183-8509, Japan.|Kariya Animal Hospital, 5-20-2 Morishita, Koto-ku, Tokyo, 135-0004, Japan.
authors.forename: Shinpei
authors.initials: S
authors.lastname: Hattori
authors.affiliation: Department of Bacteriology, Graduate school of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Hisatsune
authors.affiliation: Laboratory of Veterinary Internal Medicine, Division of Animal Life Science, Graduate School, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo, 183-8509, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Ide
authors.affiliation: Department of Bacteriology, Graduate school of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Sugai
authors.affiliation: Laboratory of Veterinary Internal Medicine, Division of Animal Life Science, Graduate School, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo, 183-8509, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nishifuji
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D007169:Impetigo / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D015603:Keratinocytes / Q000276:immunology / Q000382:microbiology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000502:physiology*; D012867:Skin / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000502:physiology*