Evidence map›Paper›PMID 16606669›Full record

ArticleThe Journal of experimental medicine2006

Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection.

Ari B Molofsky, Brenda G Byrne, Natalie N Whitfield, Cressida A Madigan, Etsu T Fuse, Kazuhiro Tateda, Michele S Swanson

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 246 papers.

0numbers the graph read from it
0cells of the map it votes in
246citing papers in PubMed
33.8field-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

246 citing papers in PubMed, 487 citations in OpenAlex.

  1. Diverse infection models demonstrate robust resistance ofbioRxiv : the preprint server for biology · 2026
    Article
  2. Regulator-derived growth and fitness costs ofbioRxiv : the preprint server for biology · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. TLR priming licenses NAIP inflammasome activation by immunoevasive ligands.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  8. Article
  9. Inflammasomes primarily restrict cytosolicbioRxiv : the preprint server for biology · 2024
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. mBio · 2023
    Article
  16. bioRxiv : the preprint server for biology · 2023
    Article
  17. Article
  18. Article
  19. Review
  20. Article

186 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

7 authors at 2 institutions in 2 countries.

Ari B MolofskyDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Brenda G Byrne
Natalie N Whitfield
Cressida A Madigan
Etsu T Fuse
Kazuhiro Tateda
Michele S Swanson
University of Michigan–Ann Arbor · USToho University · JP

Funding

CELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8M
PREDOCTORAL TRAINING IN GENETICST32GM007544 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 1985 to 2022
$11.3M
Evasion of Macrophage Lysosomes by L pneumophiliaR01AI040694 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SWANSON, MICHELE SOMES · 2003 to 2007
$1.4M
NIAID NIH HHS 2R01 AI040694NIAID NIH HHS R01 AI040694NIGMS NIH HHS T32 GM007315NIGMS NIH HHS T32 GM007544
6 · The paper itself

Abstract

To restrict infection by Legionella pneumophila, mouse macrophages require Naip5, a member of the nucleotide-binding oligomerization domain leucine-rich repeat family of pattern recognition receptors, which detect cytoplasmic microbial products. We report that mouse macrophages restricted L. pneumophila replication and initiated a proinflammatory program of cell death when flagellin contaminated their cytosol. Nuclear condensation, membrane permeability, and interleukin-1beta secretion were triggered by type IV secretion-competent bacteria that encode flagellin. The macrophage response to L. pneumophila was independent of Toll-like receptor signaling but correlated with Naip5 function and required caspase 1 activity. The L. pneumophila type IV secretion system provided only pore-forming activity because listeriolysin O of Listeria monocytogenes could substitute for its contribution. Flagellin monomers appeared to trigger the macrophage response from perforated phagosomes: once heated to disassemble filaments, flagellin triggered cell death but native flagellar preparations did not. Flagellin made L. pneumophila vulnerable to innate immune mechanisms because Naip5+ macrophages restricted the growth of virulent microbes, but flagellin mutants replicated freely. Likewise, after intratracheal inoculation of Naip5+ mice, the yield of L. pneumophila in the lungs declined, whereas the burden of flagellin mutants increased. Accordingly, macrophages respond to cytosolic flagellin by a mechanism that requires Naip5 and caspase 1 to restrict bacterial replication and release proinflammatory cytokines that control L. pneumophila infection.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsApoptosisCells, CulturedCytosolFemaleFlagellinImmunity, InnateLegionella pneumophilaMacrophagesMiceMice, Inbred AMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88Adaptor Proteins, Signal TransducingFlagellinMyd88 protein, mouseMyeloid Differentiation Factor 88Naip5 protein, mouseNeuronal Apoptosis-Inhibitory ProteinToll-Like Receptors

Identifiers

PMID16606669
PMCPMC1584282
OpenAlexW2161320421

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.