ArticleProceedings of the National Academy of Sciences of the United States of America2003
Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 297 papers, 1 of them a synthesis that pooled it.
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
297 citing papers in PubMed, 1 synthesis or guideline pooled it, 704 citations in OpenAlex.
- Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review.PloS one · 2023Pooled it
- Inflammation induced by influenza virus impairs human innate immune control of pneumococcus.Nature immunology · 2018Trial
- Influence of pathogen and focus of infection on procalcitonin values in sepsis patients with bacteremia or candidemia.Critical care (London, England) · 2018Trial
- TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization.The Journal of clinical investigation · 2015Trial
- TLR-mediated inflammatory responses to Streptococcus pneumoniae are highly dependent on surface expression of bacterial lipoproteins.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- A synopsis of competence-regulated virulence inVirulence · 2026Review
- Extracellular pneumolysin enhances the activation of cytosolic pattern-recognition receptor NOD2 through its pore-forming activity.Microbiology spectrum · 2026Article
- Streptococcus anginosus activates the NLRP3 inflammasome to promote inflammatory responses from macrophages.Journal of leukocyte biology · 2026Article
- Bacterial pore-forming toxins: mechanisms and implications for host immunity.Bioscience reports · 2026Review
- Computational Validation of Multi-Epitope mRNA Vaccine Targeting Streptococcus anginosus Surface Protein (TMPC) as an Effective Alternative Treatment to Reduce Gastric Cancer.MicrobiologyOpen · 2026Article
- Article
- Host-pathogen interaction in community-acquired pneumonia: a focus on the immune response.Frontiers in cellular and infection microbiology · 2026Review
- Vibrio cholerae cytolysin induces pro-inflammatory and death signals through novel TLR assembly.PLoS pathogens · 2025Article
- Article
- Molecular mechanisms of streptococcal disruption of the blood-brain barrier and their pathogenic role in bacterial meningitis.Frontiers in immunology · 2025Review
- Development of a broad-spectrum epitope-based vaccine against Streptococcus pneumoniae.PloS one · 2025Article
- Article
- A 3'UTR-derived small RNA represses pneumolysin synthesis and facilitates pneumococcal brain invasion.Communications biology · 2024Article
- Mucins protect against Streptococcus pneumoniae virulence by suppressing pneumolysin expression.The Journal of clinical investigation · 2024Article
- Article
237 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Streptococcus pneumoniae is one of the leading causes of invasive bacterial disease worldwide. Fragments of the cell wall and the cytolytic toxin pneumolysin have been shown to contribute substantially to inflammatory damage, although the interactions between pneumococcal components and host-cell structures have not been elucidated completely. Results of a previous study indicated that cell-wall components of pneumococci are recognized by Toll-like receptor (TLR)2 but suggested that pneumolysin induces inflammatory events independently of this receptor. In this study we tested the hypothesis that pneumolysin interacts with surface proteins of the TLR family other than TLR2. We found that pneumolysin stimulates tumor necrosis factor-alpha and IL-6 release in wild-type macrophages but not in macrophages from mice with a targeted deletion of the cytoplasmic TLR-adapter molecule myeloid differentiation factor 88, suggesting the involvement of the TLRs in pneumolysin recognition. Purified pneumolysin synergistically activated macrophage responses together with preparations of pneumococcal cell walls or staphylococcal peptidoglycan, which are known to activate TLR2. Furthermore, when compared with wild-type macrophages, macrophages from mice that carry a spontaneous mutation in TLR4 (P712H) were hyporesponsive to both pneumolysin alone and the combination of pneumolysin with pneumococcal cell walls. Finally, these TLR4-mutant mice were significantly more susceptible to lethal infection after intranasal colonization with pneumolysin-positive pneumococci than were control mice. We conclude that the interaction of pneumolysin with TLR4 is critically involved in the innate immune response to pneumococcus.
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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.