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

Shruti Naik, Nicolas Bouladoux, Jonathan L. Linehan, Seong Ji Han, Oliver J. Harrison, Christoph Wilhelm, Sean Conlan, Sarah Himmelfarb, Allyson L. Byrd, Clayton Deming, Mariam Quinones, Jason M. Brenchley, Heidi H. Kong, Roxanne Tussiwand, Kenneth M. Murphy, Miriam Merad, Julia A. Segre, Yasmine Belkaid

Research output: Contribution to journalArticlepeer-review

432 Scopus citations

Abstract

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 immunity1-4. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges5-7. 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 understanding of tissue-specific immunity and pathologies.

Original languageEnglish
Pages (from-to)104-108
Number of pages5
JournalNature
Volume520
Issue number7545
DOIs
StatePublished - Apr 2 2015

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