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. Author manuscript; available in PMC: 2023 Feb 7.
Published in final edited form as: Nat Rev Microbiol. 2022 Aug 30;21(2):97–111. doi: 10.1038/s41579-022-00780-3

Fig. 3 |. Staphylococcus epidermidis mediates skin homeostasis, barrier repair after injury and colonization resistance.

Fig. 3 |

a | Homeostasis: early-life Staphylococcus epidermidis skin colonization in the hair follicle primes the cutaneous immune response to tolerate future commensal colonization via activation of regulatory T cells (Treg cells). S. epidermidis-derived riboflavin is sensed by unconventional mucosal-associated invariant T cells (MAIT cells), priming them to become a dominant type 17 effector subset. CD11B+ dendritic cells (DCs) sense S. epidermidis healthy adult skin colonization and stimulate CD8+ T cell migration. S. epidermidis lipoteichoic acid (LTA) is sensed by dendritic cells via Toll-like receptor 2 (TLR2) signalling. S. epidermidis produces a potent sphingomyelinase (SMase) on human skin that increases ceramide content, thus promoting skin hydration and, possibly, barrier integrity. Barrier repair: S. epidermidis and its molecular products including trace amines, lipopeptide 78 and LTA dampen the inflammatory response (TNF and IL-6 production) to promote wound healing. S. epidermidis-recruited polymorphonuclear leukocytes (PMNs) stimulate plasmacytoid dendritic cells (pDCs) via CXCL10 signalling to secret type I interferons in the wound site to aid healing. CD8+ T cells express type 2 cytokines to promote wound repair. 6-N-hydroxyaminopurine (6-HAP) may also protect skin from tumour development, although further studies are necessary to clarify the mechanism and the 6-HAP biosynthetic pathway (dashed line). b | Colonization resistance: S. epidermidis excludes Group A Streptococcus (GAS) and Staphylococcus aureus from skin. Autoinducing peptides (AIPs) block S. aureus quorum sensing and the purine analogue 6-thioguanine inhibits S. aureus purine biosynthesis. S. epidermidis phenol soluble modulins (PSMs) synergize with host antimicrobial peptides (AMPs) including LL-37 to augment killing of S. aureus and GAS, although the mechanism warrants further investigation (dashed line). Unidentified secreted factors from S. epidermidis signal via TLR2 to stimulate keratinocyte production of human β-defensin 2 (hBD2) and hBD3. Unidentified S. epidermidis factors activate the keratinocyte aryl hydrocarbon receptor (AHR) and increase hBD3 expression. Some strains of S. epidermidis produce AMPs that specifically kill certain pathogenic species.