人間の皮膚：体の最初の防衛線

タイトル: Tissue resident cells differentiate S. aureus from S. epidermidis via IL-1beta following barrier disruption in healthy human skin disruption in healthy human skin

概要: The Staphylococcus species are a dominant part of the human skin microbiome and present across all body sites. Staphylococcus epidermidis is a ubiquitous skin commensal, while S. aureus is thought to colonize at least 30% of the population. S. aureus are not only colonizers but a leading cause of skin and soft tissue infections and a critical healthcare concern. To understand how healthy human skin may differentiate commensal bacteria, such as S. epidermidis, from the potential pathogen methicillin-resistant S. aureus (MRSA),, we use ex vivo human skin models that allows us to study this host-bacterial interaction in the most clinically relevant environment. Our work highlights the role of the outer stratum corneum as a protective physical barrier against invasion by colonizing Staphylococci. We show how the structural cells of the skin can internalize and respond to different Staphylococci with increasing sensitivity. Disruption of the protective stratum corneum triggered an increased and discriminative immune response led by strong IL-1{beta} expression. We identified and localized tissue resident Langerhans cells (LCs) as a potential source of this IL-1{beta} and go on to show a dose dependent response of MUTZ-LCs to S. aureus but not S. epidermidis. This suggests an important role of LCs in sensing and discriminating between bacteria in healthy human skin. This work provides a detailed snapshot of how human skin differentiates between friend and potential foe. With the rise in antibiotic resistance, understanding the innate immune response of healthy skin may help us find ways to enhance or manipulate these natural defenses to help prevent invasive infection. Author SummaryHow healthy human skin can differentiate between commensal bacteria which live harmoniously on our skin and those bacteria which have the potential to cause invasive infection is of great interest. Here we use ex vivo human skin models to show how the outer layers of human skin resists bacterial invasion and that disruption of this layer leads to increased infection and inflammation. We show how colonization of disrupted skin by the potentially pathogenic Staphyloccus aureus causes an increased IL-1{beta} signaling compared to the commensal S. epidermidis. We show that tissue resident Langerhans cells are well positioned throughout the skin epidermis and can differentiate commensal from pathogen via IL-1{beta}. This work identifies one of the subtle, yet effective pathways by which human skin differentiates commensals and pathogens. Understanding these mechanisms could lead to potential new treatment and prevention targets, mechanisms by which we can enhance innate immunity.