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

Abstract

Summary: 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. : Using a xenograft humanized model, Schulz et al. show how noninvasive colonization of the human skin corneal layer by methicillin-resistant Staphylococcus aureus (MRSA) induces a local tissue response. This response differs from the previously reported mouse models. MRSA colonization induces neutrophil recruitment to the skin, which facilitates transiency. Keywords: Staphylococcus aureus, MRSA, skin microbiota, xenograft, humanized, in vivo, neutrophils, stratum corneum, colonisation