AUTHOR=Hendriks Astrid , Mnich Malgorzata Ewa , Clemente Bruna , Cruz Ana Rita , Tavarini Simona , Bagnoli Fabio , Soldaini Elisabetta 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.642711

DOI=10.3389/fimmu.2021.642711

ISSN=1664-3224

ABSTRACT=<p>The skin is an immunocompetent tissue that harbors several kinds of immune cells and a plethora of commensal microbes constituting the skin microbiome. <italic>Staphylococcus aureus</italic> 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 <italic>S. aureus</italic> infection, however genetic and experimental evidence has shown that CD4<sup>+</sup> T cells play a key role in orchestrating a protective anti-<italic>S. aureus</italic> immune response. A high <italic>S. aureus</italic>-specific memory CD4<sup>+</sup> 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 <italic>S. aureus</italic>-specific CD4<sup>+</sup> T cells could be present in the skin of healthy individuals. Indeed, we observed proliferation of tissue-resident memory CD4<sup>+</sup> 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 <italic>S. aureus</italic>. Remarkably, these cytokines were produced also during an <italic>ex vivo</italic> epicutaneous <italic>S. aureus</italic> infection of human skin explants. These findings highlight the importance of tissue-resident memory CD4<sup>+</sup> T cells present at barrier sites such as the skin, a primary entry site for <italic>S. aureus</italic>. Further phenotypical and functional characterization of these cells will ultimately aid in the development of novel vaccine strategies against this elusive pathogen.</p>