Commensal-dendritic-cell interaction specifies a unique protective skin immune signature.

Abstract The skin represents the body’s primary interface with the environment, acting as the first line of physical and immunological defense. This organ is also home to trillions of microbes (bacteria, fungi and viruses) that play an important role in tissue homeostasis and local immunity. Skin microbial communities are highly diverse and can be remodeled over time or in response to environmental challenges. How in the context of this complexity, individual commensals may differentially modulate skin immunity and what the consequences of these responses for tissue physiology are remain unclear. Here, we demonstrate that defined commensals dominantly impact skin immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A+CD8+T cells that home to the epidermis, enhance innate barrier immunity and limit pathogen invasion. These commensal-specific T cell responses result from the coordinated action of skin resident dendritic cell subsets and are not associated with inflammation, revealing that tissue resident cells are poised to sense and respond to alterations in microbial communities. This dialogue may represent an evolutionary means by which the skin immune system uses fluctuating commensal clues to calibrate barrier immunity and provide heterologous protection against invasive pathogens. Altogether these findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodeled by encounters with defined commensals, findings that have profound implications for our understanding of tissue specific immunity and pathologies.