Related Experiment Video
Updated: May 13, 2026
A Simple and Efficient Method for Testing Immunomodulatory Agents for Generation of Tolerogenic Dendritic Cells from Human CD14+ Monocytes
Published on: April 11, 2025
Staphylococcus aureus phenol-soluble modulin peptides modulate dendritic cell functions and increase in vitro priming
Jens Schreiner1, Dorothee Kretschmer, Juliane Klenk
1Interfaculty Institute for Cell Biology, Eberhard Karls University, 72076 Tübingen, Germany.
Abstract:
The major human pathogen Staphylococcus aureus has very efficient strategies to subvert the human immune system. Virulence of the emerging community-associated methicillin-resistant S. aureus depends on phenol-soluble modulin (PSM) peptide toxins, which are known to attract and lyse neutrophils. However, their influences on other immune cells remain elusive. In this study, we analyzed the impact of PSMs on dendritic cells (DCs) playing an essential role in linking innate and adaptive immunity. In human neutrophils, PSMs exert their function by binding to the formyl peptide receptor (FPR) 2. We show that mouse DCs express the FPR2 homolog mFPR2 as well as its paralog mFPR1 and that PSMs are chemoattractants for DCs at noncytotoxic concentrations. PSMs reduced clathrin-mediated endocytosis and inhibited TLR2 ligand-induced secretion of the proinflammatory cytokines TNF, IL-12, and IL-6, while inducing IL-10 secretion by DCs. As a consequence, treatment with PSMs impaired the capacity of DCs to induce activation and proliferation of CD4(+) T cells, characterized by reduced Th1 but increased frequency of FOXP3(+) regulatory T cells. These regulatory T cells secreted high amounts of IL-10, and their suppression capacity was dependent on IL-10 and TGF-β. Interestingly, the induction of tolerogenic DCs by PSMs appeared to be independent of mFPRs, as shown by experiments with mice lacking mFPR2 (mFPR2(-/-)) and the cognate G protein (p110γ(-/-)). Thus, PSMs from highly virulent pathogens affect DC functions, thereby modulating the adaptive immune response and probably increasing the tolerance toward the pathogen.
Insights
Phenol-soluble modulin (PSM) peptide toxins from Staphylococcus aureus impact dendritic cells (DCs), reducing pro-inflammatory responses and promoting regulatory T cells. This modulation of immune cells may increase pathogen tolerance.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Staphylococcus aureus is a major human pathogen with immune evasion strategies.
- Phenol-soluble modulin (PSM) peptide toxins are key virulence factors of S. aureus, known to affect neutrophils.
- The impact of PSMs on other immune cells, particularly dendritic cells (DCs), remains largely unknown.
Purpose of the Study:
- To investigate the effects of PSMs on dendritic cell (DC) function.
- To determine the role of PSMs in modulating adaptive immunity.
- To elucidate the mechanisms by which PSMs influence immune cell interactions.
Main Methods:
- Analysis of PSM interaction with mouse dendritic cells (DCs) expressing mFPR1 and mFPR2.
- Assessment of DC chemoattraction, endocytosis, and cytokine secretion in response to PSMs.
- Evaluation of DC-mediated T cell activation, proliferation, and differentiation.
- Experiments using mFPR2 knockout mice to assess receptor-dependent effects.
Main Results:
- PSMs act as chemoattractants for DCs at non-cytotoxic concentrations.
- PSMs inhibit clathrin-mediated endocytosis and pro-inflammatory cytokine secretion (TNF, IL-12, IL-6) by DCs.
- PSMs induce IL-10 secretion by DCs, leading to the generation of FOXP3(+) regulatory T cells.
- PSM-induced tolerogenic DCs impair CD4(+) T cell activation and promote Th1 suppression.
- The induction of tolerogenic DCs by PSMs is independent of mFPR2 and p110γ.
Conclusions:
- PSMs from S. aureus significantly impact DC function, promoting a tolerogenic immune response.
- PSMs modulate DC cytokine profiles and T cell differentiation, favoring regulatory T cells.
- These findings suggest a mechanism by which S. aureus may increase host tolerance to infection.
- The mFPR-independent pathway highlights a novel aspect of PSM-mediated immune modulation.
Related Concept Videos
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:31Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
01:22Antigen Presenting Cells
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
01:40Cell-mediated Immune Responses