Evidence map›Paper›PMID 20133635›Full record

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.

Edward A Miao, Dat P Mao, Natalya Yudkovsky, Richard Bonneau, Cynthia G Lorang, Sarah E Warren, Irina A Leaf, Alan Aderem

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
454citing papers in PubMed
32.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

454 citing papers in PubMed, 787 citations in OpenAlex.

  1. Review
  2. Pyroptosis: Molecular mechanisms and function.Journal of physiology and biochemistry · 2026
    Review
  3. Review
  4. Article
  5. Regulator-derived growth and fitness costs ofbioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  10. Article
  11. Article
  12. Review
  13. Frontiers in immunology · 2026
    Article
  14. Article
  15. Review
  16. Article
  17. Human non-canonical inflammasomes activate CASP3 to limit intracellularbioRxiv : the preprint server for biology · 2025
    Article
  18. Review
  19. Innate detection ofbioRxiv : the preprint server for biology · 2025
    Article
  20. Review

394 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Edward A MiaoInstitute for Systems Biology, Seattle, WA 98103, USA.
Dat P Mao
Natalya Yudkovsky
Richard Bonneau
Cynthia G Lorang
Sarah E Warren
Irina A Leaf
Alan Aderem
Institute for Systems Biology · USNew York University · USUniversity of Washington · US

Funding

Variation in Human Innate ImmunityU54AI057141 · NIAID · UNIVERSITY OF WASHINGTON · PI WURFEL, MARTIN M. · 2003 to 2013
$102.3M
LPS Signaling in Macrophages: The Roll of TollR01AI032972 · NIAID · UNIVERSITY OF WASHINGTON · PI ADEREM, ALAN A · 1992 to 2020
$14.6M
LPS REGULATION OF MACROPHAGE FUNCTIONR01AI025032 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI ADEREM, ALAN A · 1987 to 2016
$6.7M
Recognition of Bacterial Flagellin by MacrophagesR01AI052286 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI ADEREM, ALAN A · 2002 to 2011
$4.2M
LPS REGULATION OF MACROPHAGE FUNCTIONR37AI025032 · NIAID · UNIVERSITY OF WASHINGTON · PI ADEREM, ALAN A · 1995 to 2004
$2.4M
Ipaf signaling in innate immunityK08AI065878 · NIAID · INSTITUTE FOR SYSTEMS BIOLOGY · PI MIAO, EDWARD A · 2005 to 2008
$512k
NIAID NIH HHS AI025032NIAID NIH HHS AI032972NIAID NIH HHS AI052286NIAID NIH HHS AI065878NIAID NIH HHS K08 AI065878NIAID NIH HHS R01 AI025032NIAID NIH HHS R01 AI032972NIAID NIH HHS R01 AI052286NIAID NIH HHS R37 AI025032NIAID NIH HHS U54 AI057141NIAID NIH HHS U54AI057141
6 · The paper itself

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.

Indexed as

AnimalsApoptosis Regulatory ProteinsBacterial InfectionsBacterial ProteinsCalcium-Binding ProteinsCaspase 1Immunity, InnateMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutProtein ConformationTransfectionApoptosis Regulatory ProteinsBacterial ProteinsCalcium-Binding ProteinsCaspase 1Ipaf protein, mouseMembrane ProteinsSpi1 protein, SalmonellaSPI-2 protein, Salmonella

Identifiers

PMID20133635
PMCPMC2840275
OpenAlexW2155538302

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.