Neutrophil Recruitment to Noninvasive MRSA at the Stratum Corneum of Human Skin Mediates Transient Colonization

Cell Rep. 2019 Oct 29;29(5):1074-1081.e5. doi: 10.1016/j.celrep.2019.09.055.

Abstract

Staphylococcus aureus is a leading cause of skin and soft issue infection, but paradoxically, it also transiently, and often harmlessly, colonizes human skin. An obstacle to understanding this contradiction has been a shortage of in vivo models reproducing the unique structure and immunology of human skin. In this work, we developed a humanized model to study how healthy adult human skin responds to colonizing methicillin-resistant S. aureus (MRSA). We demonstrate the importance of the outer stratum corneum as the major site of bacterial colonization and how noninvasive MRSA adhesion to corneocytes induces a local inflammatory response in underlying skin layers. This signaling recruits neutrophils to the skin, where they control bacterial numbers, mediating transiency in colonization. This work highlights the spatiotemporal aspects of human skin colonization and demonstrates a subclinical inflammatory response to noninvasive MRSA that allows human skin to regulate the bacterial population at its outer surface.

Keywords: MRSA; Staphylococcus aureus; colonisation; humanized; in vivo; neutrophils; skin microbiota; stratum corneum; xenograft.

MeSH terms

  • Animals
  • Colony Count, Microbial
  • Dermis / microbiology
  • Dermis / pathology
  • Epidermis / microbiology
  • Epidermis / pathology
  • Female
  • Heterografts
  • Humans
  • Inflammation / microbiology
  • Inflammation / pathology
  • Interleukin-8 / metabolism
  • Male
  • Methicillin-Resistant Staphylococcus aureus / growth & development*
  • Mice, SCID
  • Models, Biological
  • Neutrophil Infiltration*
  • Skin / microbiology*
  • Skin / pathology
  • Staphylococcal Skin Infections / microbiology
  • Staphylococcal Skin Infections / pathology
  • Up-Regulation

Substances

  • Interleukin-8