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The skin is an immunocompetent tissue that harbors several kinds of immune cells and a plethora of commensal microbes constituting the skin microbiome.  Staphylococcus aureus  is a prominent skin pathogen that colonizes a large proportion of the human population. We currently have an incomplete understanding of the correlates of protection against  S. aureus  infection, however genetic and experimental evidence has shown that CD4 +  T cells play a key role in orchestrating a protective anti- S. aureus  immune response. A high  S. aureus -specific memory CD4 +  T cell response has been reported in the blood of healthy subjects. Since T cells are more abundant in the skin than in blood, we hypothesized that  S. aureus -specific CD4 +  T cells could be present in the skin of healthy individuals. Indeed, we observed proliferation of tissue-resident memory CD4 +  T cells and production of IL-17A, IL-22, IFN-γ and TNF-β by cells isolated from abdominal skin explants in response to heat-killed  S. aureus . Remarkably, these cytokines were produced also during an  ex vivo  epicutaneous  S. aureus  infection of human skin explants. These findings highlight the importance of tissue-resident memory CD4 +  T cells present at barrier sites such as the skin, a primary entry site for  S. aureus . Further phenotypical and functional characterization of these cells will ultimately aid in the development of novel vaccine strategies against this elusive pathogen.

Staphylococcus aureus-Specific Tissue-Resident Memory CD4+ T Cells Are Abundant in Healthy Human Skin