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

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.

The composition of the microbiota modulates allograft rejection

“…Thus, it is yet unclear whether it is the microbial constituents of the intestine or of the skin that can promote alloreactivity. Indeed, defined skin commensals have recently been shown to modify local cutaneous immunity, affecting skin DCs and resident T cells and enhancing barrier immunity (13). The intestinal microbiota have also been shown to affect immunity as distal as the peripheral joints or the central nervous system in models of autoimmune arthritis or autoimmune encephalomyelitis (14,15).…”

Tissue-Resident Memory T Cells and Fixed Immune Surveillance in Nonlymphoid Organs

“…The combination of local immune surveillance in low-inflammatory settings brings into play other scenarios, such as infection with commensal microorganisms. Naik et al (87) showed that skin infection with selected strains of the commensal bacteria Staphylococcus epididymis resulted in accumulation of IL-17-producing, intraepithelial CD8 + CD103 + T cells in the absence of overt inflammation. Although the experiments did not formally identify these as CD8 + T RM cells, their intraepithelial localization and CD103 expression heavily implied that they were indeed nonmigratory memory cells sequestered from the circulation.…”

The intersection of microbiome and host at the skin interface: genomic- and metagenomic-based insights

“…Employing laser capture microdissection of these compartments followed by 16S rRNA sequencing, Nakatsuji et al (2013) provided a potential mechanism by which microbes or their products may physically interact with immune cells in tissues previously believed to be sterile in order to exert an effect on the host. Indeed, colonization with a human commensal skin microbe, namely, Staphylococcus epidermidis, tunes T-cell homing and function in an IL-1-dependent manner in mice (Naik et al 2012(Naik et al , 2015. On the other hand, deficiencies in immunity have been shown in humans and mice to result in altered cutaneous microbial communities (Chehoud et al 2013;Oh et al 2013).…”