Evidence map›Paper›PMID 24739967›Full record

ArticleNature2014

Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread.

Mark A Czuczman, Ramzi Fattouh, Jorik M van Rijn, Veronica Canadien, Suzanne Osborne, Aleixo M Muise, Vijay K Kuchroo, Darren E Higgins, John H Brumell

Open access · greenAbstract read
In one paragraph

Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

95 citing papers in PubMed, 151 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Differential virulence gene carriage inFrontiers in microbiology · 2026
    Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Cell Death and Infection: Implications for Host and Microbe.Advances in experimental medicine and biology · 2025
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

Mark A Czuczman1] Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G0A4, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S1A8, Canada.
Ramzi FattouhCell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G0A4, Canada.
Jorik M van RijnDepartment of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
Veronica CanadienCell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G0A4, Canada.
Suzanne OsborneCell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G0A4, Canada.
Aleixo M Muise1] Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G0A4, Canada [2] Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, Hospital for Sick Children, Toronto, Ontario M5G1X8, Canada [3] Institute of Medical Science, University of Toronto, Toronto, Ontario M5S1A8, Canada [4] Sickkids IBD Centre, Hospital for Sick Children, Toronto, Ontario M5G1X8, Canada.
Vijay K KuchrooCenter for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Darren E HigginsDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
John H Brumell1] Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G0A4, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S1A8, Canada [3] Institute of Medical Science, University of Toronto, Toronto, Ontario M5S1A8, Canada [4] Sickkids IBD Centre, Hospital for Sick Children, Toronto, Ontario M5G1X8, Canada.
Hospital for Sick Children · CAHarvard University · USUniversity Medical Center Utrecht · NLUniversity of Toronto · CA

Funding

Temporal Requirements for Intracellular PathogenesisR01AI053669 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI HIGGINS, DARREN E · 2003 to 2012
$3.5M
Role of Tim-4 in Regulating Type 1 DiabetesR01DK096138 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI KUCHROO, VIJAY K. · 2013 to 2016
$1.4M
CIHRNIAID NIH HHS AI053669NIAID NIH HHS R01 AI053669NIDDK NIH HHS R01 DK096138
6 · The paper itself

Abstract

Efferocytosis, the process by which dying or dead cells are removed by phagocytosis, has an important role in development, tissue homeostasis and innate immunity. Efferocytosis is mediated, in part, by receptors that bind to exofacial phosphatidylserine (PS) on cells or cellular debris after loss of plasma membrane asymmetry. Here we show that a bacterial pathogen, Listeria monocytogenes, can exploit efferocytosis to promote cell-to-cell spread during infection. These bacteria can escape the phagosome in host cells by using the pore-forming toxin listeriolysin O (LLO) and two phospholipase C enzymes. Expression of the cell surface protein ActA allows L. monocytogenes to activate host actin regulatory factors and undergo actin-based motility in the cytosol, eventually leading to formation of actin-rich protrusions at the cell surface. Here we show that protrusion formation is associated with plasma membrane damage due to LLO's pore-forming activity. LLO also promotes the release of bacteria-containing protrusions from the host cell, generating membrane-derived vesicles with exofacial PS. The PS-binding receptor TIM-4 (encoded by the Timd4 gene) contributes to efficient cell-to-cell spread by L. monocytogenes in macrophages in vitro and growth of these bacteria is impaired in Timd4(-/-) mice. Thus, L. monocytogenes promotes its dissemination in a host by exploiting efferocytosis. Our results indicate that PS-targeted therapeutics may be useful in the fight against infections by L. monocytogenes and other bacteria that use similar strategies of cell-to-cell spread during infection.

Indexed as

PhagocytosisActinsAnimalsBacterial ToxinsCell MembraneCell Surface ExtensionsCytoplasmFemaleHeat-Shock ProteinsHeLa CellsHemolysin ProteinsHumansListeria monocytogenesMacrophagesMembrane ProteinsMiceActinsBacterial ToxinsHeat-Shock ProteinsHemolysin ProteinshlyA protein, Listeria monocytogenesMembrane ProteinsPhosphatidylserinesTIM-4 protein, mouseType C Phospholipases

Identifiers

PMID24739967
PMCPMC4151619
OpenAlexW2120778262

What OpenQuestion holds

Textmetadata
LicenceTDM
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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.