ArticleProceedings of the National Academy of Sciences of the United States of America2010
Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 454 papers.
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Who cites it
454 citing papers in PubMed, 787 citations in OpenAlex.
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
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- Global research trends, knowledge structure, and future directions in melioidosis research: a bibliometric analysis, 1990-2025.Tropical medicine and health · 2026Article
- Regulator-derived growth and fitness costs ofbioRxiv : the preprint server for biology · 2026Article
- Human non-canonical inflammasomes activate CASP3 to limit intracellular Salmonella replication in macrophages.PLoS pathogens · 2026Article
- Host response to bacteria induces a shift towards the enteroendocrine cell lineage in the murine enteroid model.PLoS pathogens · 2026Article
- Gasdermins against intracellular bacterial pathogens.Nature microbiology · 2026Review
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- Environmental Amino Acid Sensing Regulates the Rate of ASC Translation and NLRP3 Inflammasome Assembly.bioRxiv : the preprint server for biology · 2026Article
- Dual NLRC4 and non-canonical inflammasome signaling drives human GSDMD-mediated killing ofbioRxiv : the preprint server for biology · 2026Article
- Targeting inflammasome, IL-1β, and coagulation in melioidosis.Frontiers in microbiology · 2026Review
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- NLRC4 and NLRP3 in tissues as potential biomarkers for the diagnosis of non-small cell lung cancer in pulmonary tuberculosis.Frontiers in cellular and infection microbiology · 2026Article
- Cytosolic receptors and signaling in antifungal immunity.The EMBO journal · 2025Review
- Profile of NT-0527, a brain penetrant NLRP3 Inflammasome inhibitor suitable as anRSC medicinal chemistry · 2025Article
- Human non-canonical inflammasomes activate CASP3 to limit intracellularbioRxiv : the preprint server for biology · 2025Article
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Innate detection ofbioRxiv : the preprint server for biology · 2025Article
- The Role of Inflammasomes in LPS and Gram-Negative Bacterial Sepsis.Journal of clinical medicine · 2025Review
394 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The mammalian innate immune system uses Toll-like receptors (TLRs) and Nod-LRRs (NLRs) to detect microbial components during infection. Often these molecules work in concert; for example, the TLRs can stimulate the production of the proforms of the cytokines IL-1beta and IL-18, whereas certain NLRs trigger their subsequent proteolytic processing via caspase 1. Gram-negative bacteria use type III secretion systems (T3SS) to deliver virulence factors to the cytosol of host cells, where they modulate cell physiology to favor the pathogen. We show here that NLRC4/Ipaf detects the basal body rod component of the T3SS apparatus (rod protein) from S. typhimurium (PrgJ), Burkholderia pseudomallei (BsaK), Escherichia coli (EprJ and EscI), Shigella flexneri (MxiI), and Pseudomonas aeruginosa (PscI). These rod proteins share a sequence motif that is essential for detection by NLRC4; a similar motif is found in flagellin that is also detected by NLRC4. S. typhimurium has two T3SS: Salmonella pathogenicity island-1 (SPI1), which encodes the rod protein PrgJ, and SPI2, which encodes the rod protein SsaI. Although PrgJ is detected by NLRC4, SsaI is not, and this evasion is required for virulence in mice. The detection of a conserved component of the T3SS apparatus enables innate immune responses to virulent bacteria through a single pathway, a strategy that is divergent from that used by plants in which multiple NB-LRR proteins are used to detect T3SS effectors or their effects on cells. Furthermore, the specific detection of the virulence machinery permits the discrimination between pathogenic and nonpathogenic bacteria.
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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.