Evidence map›Paper›PMID 27045008›Full record

ArticleThe Journal of experimental medicine2016

NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo.

Isabella Rauch, Jeannette L Tenthorey, Randilea D Nichols, Khatoun Al Moussawi, James J Kang, Chulho Kang, Barbara I Kazmierczak, Russell E Vance

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
10.8field-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

76 citing papers in PubMed, 108 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. An overview of human inflammasomes: Activation and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2026
    Review
  5. NLRP1B is an integrated decoy that subvertsProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. Article
  9. The IL-18 receptor is expressed on murine small-intestinal enterochromaffin cells and executes a recovery program upon injury.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Article
  12. TLR priming licenses NAIP inflammasome activation by immunoevasive ligands.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  13. Article
  14. Inflammasomes primarily restrict cytosolicbioRxiv : the preprint server for biology · 2024
    Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. mBio · 2023
    Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Isabella RauchDivision of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720.
Jeannette L TenthoreyDivision of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720.
Randilea D NicholsDivision of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720.
Khatoun Al MoussawiDepartment of Medicine, Yale University School of Medicine, New Haven, CT 06510.
James J KangDivision of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720.
Chulho KangCancer Research Laboratory, University of California, Berkeley, Berkeley, CA 94720.
Barbara I KazmierczakDepartment of Medicine, Yale University School of Medicine, New Haven, CT 06510 Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510.
Russell E VanceDivision of Immunology and Pathogenesis, University of California, Berkeley, Berkeley, CA 94720 Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720 Cancer Research Laboratory, University of California, Berkeley, Berkeley, CA 94720 rvance@berkeley.edu.
University of California, Berkeley · USYale University · USHoward Hughes Medical Institute · US

Funding

The role of Listeria cyclic-di-AMP during infection and immunityP01AI063302 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI STANLEY, SARAH A · 2004 to 2025
$45.5M
Functional and Structural Dissection of Inflammasome ActivationR37AI075039 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI RUSSELL E VANCE · 2018 to 2026
$3.8M
Specificity and in vivo function of the Naip/Nlrc4 inflammasomesR01AI075039 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI VANCE, RUSSELL E · 2008 to 2017
$3.6M
Innate Immune Responses to Type 3 Secretion System Components and EffectorsR01AI081825 · NIAID · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 2010 to 2013
$1.7M
Austrian Science Fund FWF J 3789Howard Hughes Medical InstituteNIAID NIH HHS P01 AI063302NIAID NIH HHS R01 AI075039NIAID NIH HHS R01 AI081825NIAID NIH HHS R37 AI075039
6 · The paper itself

Abstract

NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]-containing proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR family, apoptosis inhibitory proteins) are NLRs that appear to function as cytosolic immunoreceptors for specific bacterial proteins, including flagellin and the inner rod and needle proteins of bacterial type III secretion systems (T3SSs). Despite strong biochemical evidence implicating NAIPs in specific detection of bacterial ligands, genetic evidence has been lacking. Here we report the use of CRISPR/Cas9 to generate Naip1(-/-) and Naip2(-/-) mice, as well as Naip1-6(Δ/Δ) mice lacking all functional Naip genes. By challenging Naip1(-/-) or Naip2(-/-) mice with specific bacterial ligands in vivo, we demonstrate that Naip1 is uniquely required to detect T3SS needle protein and Naip2 is uniquely required to detect T3SS inner rod protein, but neither Naip1 nor Naip2 is required for detection of flagellin. Previously generated Naip5(-/-) mice retain some residual responsiveness to flagellin in vivo, whereas Naip1-6(Δ/Δ) mice fail to respond to cytosolic flagellin, consistent with previous biochemical data implicating NAIP6 in flagellin detection. Our results provide genetic evidence that specific NAIP proteins function to detect specific bacterial proteins in vivo.

Indexed as

AnimalsBacteriaFlagellinMiceMice, KnockoutNeuronal Apoptosis-Inhibitory ProteinType III Secretion SystemsFlagellinNaip1 protein, mouseNaip2 protein, mouseNaip5 protein, mouseNeuronal Apoptosis-Inhibitory ProteinType III Secretion Systems

Identifiers

PMID27045008
PMCPMC4854734
OpenAlexW2338575567

What OpenQuestion holds

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LicenceCC BY-NC-SA
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Registered trials

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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.