ArticlemBio2022
Proteolytic Activity-Independent Activation of the Immune Response by Gingipains from Porphyromonas gingivalis.
Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- Review
- Periodontitis and Chronic Liver Disease: Mechanistic Insights Focusing onMicroorganisms · 2026Review
- Investigation of a viable but non-culturable state in Porphyromonas gingivalis and host cell invasion.PloS one · 2026Article
- Novel small molecule targeting PgQC reducesFrontiers in oral health · 2026Article
- The bidirectional effects and mechanisms of the oral and gut microbiomes: a narrative review.Frontiers in immunology · 2026Review
- Oral and Gut Health, (Neuro) Inflammation, and Central Sensitization in Chronic Pain: A Narrative Review of Mechanisms, Treatment Opportunities, and Research Agenda.International journal of molecular sciences · 2025Review
- Lys-specific gingipain (Kgp) ofmBio · 2025Article
- The Role of Oral and Gut Microbiota in Bone Health: Insights from Bacterial Extracellular Vesicles.Microorganisms · 2025Review
- Discovery of Gingipains andFoods (Basel, Switzerland) · 2025Review
- Exploring the Oral Microbiome: Understanding its Impact on the Development of Oral Squamous Cell Carcinoma.Current microbiology · 2025Review
- Periodontal Microbial Profiles Across Periodontal Conditions in Pediatric Subjects: A Narrative Review.Microorganisms · 2025Review
- Oral microbiota and respiratory diseases: advances and perspectives.Clinical microbiology reviews · 2025Review
- Periodontal Status and Herpesiviridae, Bacteria, and Fungi in Gingivitis and Periodontitis of Systemically Compromised Pediatric Subjects: A Systematic Review.Children (Basel, Switzerland) · 2025Review
- The efficacy of antimicrobial therapies in the treatment of mixed biofilms formed between Candida albicans and Porphyromonas gingivalis during epithelial cell infection in the aspiration pneumonia model.Medical microbiology and immunology · 2025Article
- Microbiological and molecular aspects of periodontitis pathogenesis: an infection-induced inflammatory condition.Frontiers in cellular and infection microbiology · 2025Review
- Outer Membrane Vesicles Derived from Oral Bacteria Act as a Dagger in Host Immunity: Insight Tips from Local Diseases to Systemic Effects.International journal of biological sciences · 2025Review
- Linking microbial communities to rheumatoid arthritis: focus on gut, oral microbiome and their extracellular vesicles.Frontiers in immunology · 2025Review
- Oral Pathobiont-Derived Outer Membrane Vesicles in the Oral-Gut Axis.International journal of molecular sciences · 2024Review
- Investigating the role of aFrontiers in oral health · 2024Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Porphyromonas gingivalis, a keystone pathogen in periodontitis (PD), produces cysteine proteases named gingipains (RgpA, RgpB, and Kgp), which strongly affect the host immune system. The range of action of gingipains is extended by their release as components of outer membrane vesicles, which efficiently diffuse into surrounding gingival tissues. However, away from the anaerobic environment of periodontal pockets, increased oxygen levels lead to oxidation of the catalytic cysteine residues of gingipains, inactivating their proteolytic activity. In this context, the influence of catalytically inactive gingipains on periodontal tissues is of significant interest. Here, we show that proteolytically inactive RgpA induced a proinflammatory response in both gingival keratinocytes and dendritic cells. Inactive RgpA is bound to the cell surface of gingival keratinocytes in the region of lipid rafts, and using affinity chromatography, we identified RgpA-interacting proteins, including epidermal growth factor receptor (EGFR). Next, we showed that EGFR interaction with inactive RgpA stimulated the expression of inflammatory cytokines. The response was mediated via the EGFR-phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, which when activated in the gingival tissue rich in dendritic cells in the proximity of the alveolar bone, may significantly contribute to bone resorption and the progress of PD. Taken together, these findings broaden our understanding of the biological role of gingipains, which in acting as proinflammatory factors in the gingival tissue, create a favorable milieu for the growth of inflammophilic pathobionts.
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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.