title: The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa.
abstract: BACKGROUND
  Peptide antibiotics are part of the surface defences against microbial intruders. However, the presence and significance of these innate immune effectors in the skin barrier of the newborn infant have not yet been appreciated. Erythema toxicum neonatorum is an inflammatory skin reaction of unknown aetiology and significance, commonly present in the healthy newborn infant.
  
  
  OBJECTIVE
  As peptide antibiotics are upregulated in inflammatory skin disorders, we hypothesized that this also could be the case in erythema toxicum. We also investigated if the vernix caseosa, a cream-like white substance present on the skin of the infant at birth, might contribute to host defences.
  
  
  METHODS
  The presence of the human antibacterial peptide LL-37 was investigated by immunohistochemistry and confocal imaging of skin biopsies from four 1-day-old infants with an erythema toxicum rash and four matched newborns without the rash. In addition, we analysed the expression of LL-37 and human beta defensin-1, an antibacterial peptide of epithelial origin, by reverse transcriptase-polymerase chain reaction. Finally, we screened for antibacterial components in vernix material obtained from six healthy newborns by inhibition zone assays.
  
  
  RESULTS
  All biopsies from the lesions of erythema toxicum showed a dense, nodular infiltrate with numerous LL-37-expressing cells located in the dermal layer and a clear localization of the peptide within CD15-expressing neutrophils, EG2-expressing eosinophils and CD1a-expressing dendritic cells. LL-37 was also found to be located in CD1a-expressing Langerhans cells and a positive staining for the peptide was seen throughout the whole epidermal layer, both in infants with and without the rash. Skin samples from infants with the rash of erythema toxicum showed a constitutive expression of human beta defensin-1, while the expression of LL-37 seemed to be induced. Furthermore, LL-37 and lysozyme were detected in the protein fractions derived from the vernix caseosa, and these fractions exhibited a clear antibacterial activity.
  
  
  CONCLUSIONS
  Peptide antibiotics are present in the vernix caseosa and in the skin of the healthy newborn infant, indicating effective innate immune protection already during fetal and neonatal life.
authors.affiliation: Department of Woman and Child Health, Astrid Lindgren Children's Hospital, Karolinska Hospital C4:U1, Karolinska Institutet, S-171 76 Stockholm, Sweden. giovanna.marchini@ks.se.
authors.forename: G
authors.initials: G
authors.lastname: Marchini
authors.forename: S
authors.initials: S
authors.lastname: Lindow
authors.forename: H
authors.initials: H
authors.lastname: Brismar
authors.forename: B
authors.initials: B
authors.lastname: Ståbi
authors.forename: V
authors.initials: V
authors.lastname: Berggren
authors.forename: A-K
authors.initials: AK
authors.lastname: Ulfgren
authors.forename: S
authors.initials: S
authors.lastname: Lonne-Rahm
authors.forename: B
authors.initials: B
authors.lastname: Agerberth
authors.forename: G H
authors.initials: GH
authors.lastname: Gudmundsson
mesh_terms: D000900:Anti-Bacterial Agents / Q000032:analysis*; D015153:Blotting, Western; D004890:Erythema / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn / Q000276:immunology*; D008297:Male; D018613:Microscopy, Confocal; D010455:Peptides; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology*; D014708:Vernix Caseosa / Q000276:immunology*
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides