ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Staphylococcus aureus phenol-soluble modulin peptides modulate dendritic cell functions and increase in vitro priming of regulatory T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- Safety and immunogenicity of an investigational 4-component Staphylococcus aureus vaccine with or without AS03B adjuvant: Results of a randomized phase I trial.Human vaccines & immunotherapeutics · 2015Trial
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- LinkingAntibiotics (Basel, Switzerland) · 2024Review
- The role of Staphylococcus aureus quorum sensing in cutaneous and systemic infections.Inflammation and regeneration · 2024Review
- Phenol-Soluble Modulin α3 Stimulates Autophagy in HaCaT Keratinocytes.Biomedicines · 2023Article
- Phenol-soluble modulin α and β display divergent roles in mice with staphylococcal septic arthritis.Communications biology · 2022Article
- Integrating complex host-pathogen immune environments into S. aureus vaccine studies.Cell chemical biology · 2022Review
- The Role of the Oral Immune System in Oropharyngeal Candidiasis-Facilitated Invasion and Dissemination ofFrontiers in oral health · 2022Review
- Pharmacological Mechanisms of Shangke Huangshui against Skin and Soft Tissue Infection.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Staphylococcus aureus PSMs are a double-edged sword.Nature microbiology · 2022Article
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- Review
- Identification of a Quorum Sensing-Dependent Communication Pathway Mediating Bacteria-Gut-Brain Cross Talk.iScience · 2020Article
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- Article
- Toxin-Triggered Interleukin-1 Receptor Signaling Enables Early-Life Discrimination of Pathogenic versus Commensal Skin Bacteria.Cell host & microbe · 2019Article
- Article
- PSM Peptides From Community-Associated Methicillin-ResistantFrontiers in immunology · 2019Article
- Survival of Staphylococcus epidermidis in Fibroblasts and Osteoblasts.Infection and immunity · 2018Article
- Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.