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Updated: Aug 21, 2026
Lymphocyte Isolation from Human Skin for Phenotypic Analysis and Ex Vivo Cell Culture
Published on: April 8, 2016
PSMε controls skin commensal CD8 + T cell activation
Abstract:
Upon skin colonization, the prevalent human skin commensal S. epidermidis can elicit a CD8 + T cell response that protects against pathogens or clears tumors. The microbial features that drive this response are undefined, limiting our ability to understand and predict commensal-immune crosstalk and to engineer potent commensal-derived immunotherapies. To uncover these microbial features, we harnessed both the natural variation in CD8 + T cell induction across primary human isolates of Staphylococcus and our ability to genetically manipulate these strains. Stimulatory strains exhibit increased quorum sensing activation, which turns on a unique commensal-associated gene family, called phenol-soluble modulin ε (PSMε), that is required for CD8 + T cell activation. PSMε not only acts as the immunodominant CD8 + T cell antigen but also enhances cross-presentation in an antigen-agnostic manner. Co-delivering PSMε promotes CD8 + T cell priming to an exogenous antigen via a mechanism that is independent of formyl peptide receptor and co-stimulatory receptor upregulation. Thus, we demonstrate that specific aspects of microbiome-immune crosstalk can be distilled to molecular components, which engage in previously undescribed mechanisms and can be harnessed for immunotherapy without requiring live bacterial colonization.
Insights
Certain Staphylococcus epidermidis strains activate CD8+ T cells via phenol-soluble modulin ε (PSMε). This molecule can be harnessed for immunotherapy, enhancing T cell responses without live bacteria.
Area of Science:
- Microbiology
- Immunology
- Biotechnology
Background:
- The human skin commensal Staphylococcus epidermidis can induce CD8+ T cell responses beneficial for pathogen defense and tumor clearance.
- Understanding the specific microbial factors driving these responses is crucial for developing commensal-derived immunotherapies.
Purpose of the Study:
- To identify the microbial features of S. epidermidis responsible for eliciting CD8+ T cell responses.
- To explore the potential of these features for novel immunotherapy strategies.
Main Methods:
- Investigated natural variation in CD8+ T cell induction across primary human S. epidermidis isolates.
- Utilized genetic manipulation of bacterial strains to identify key molecular components.
- Assessed the role of quorum sensing and specific gene families in T cell activation.
Main Results:
- Increased quorum sensing activation in stimulatory strains correlated with the upregulation of phenol-soluble modulin ε (PSMε).
- PSMε was identified as essential for CD8+ T cell activation and acts as an immunodominant antigen.
- PSMε enhanced antigen cross-presentation independently of bacterial presence, promoting T cell priming.
Conclusions:
- Microbiome-immune interactions can be simplified to specific molecular components like PSMε.
- PSMε engages novel mechanisms to enhance T cell responses and can be utilized for immunotherapy without requiring live bacterial colonization.
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