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

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-1beta expression. We identified and localized tissue resident Langerhans cells (LCs) as a potential source of this IL-1beta 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.