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

Defined skin commensal bacteria elicit a dermal dendritic-cell-dependent, long-lasting, commensal-specific CD8 + T-cell response that promotes protection against pathogens while preserving tissue homeostasis. Interactions between skin bacteria and the immune system The importance of our gut microbiota in health and disease is well established. Less clear is the role of the commensal microbes on the skin, where they interact with a tissue that, unlike the gut, is not designed for absorption. Here Yasmine Belkaid and colleagues examine the nature of the antigen presenting cells involved in the dialogue between the immune system and skin commensals. They find that defined skin commensal bacteria elicit a dermal dendritic-cell-dependent, long-lasting and commensal-specific CD8 + T-cell response, while preserving tissue homeostasis. The CD8 + T cells are shown to enhance innate protection against a fungal pathogen. The skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local immunity 1 , 2 , 3 , 4 . Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges 5 , 6 , 7 . How, in the context of this complexity, individual commensal microorganisms may differentially modulate skin immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect 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. 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 interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understandi