Evidence map›Paper›PMID 32514064›Full record

ArticleNature immunology2020

Interferon-mediated reprogramming of membrane cholesterol to evade bacterial toxins.

Quan D Zhou, Xun Chi, Min Sub Lee, Wei Yuan Hsieh, Jonathan J Mkrtchyan, An-Chieh Feng, Cuiwen He, Autumn G York, Viet L Bui, Eliza B Kronenberger and 10 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
12.1field-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

66 citing papers in PubMed, 96 citations in OpenAlex.

  1. Trial
  2. Article
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  5. Visualization of the interaction between sphingomyelin and cholesterol in lipid bilayer membranes.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  10. Review
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  17. Monitoring Accessible Cholesterol Levels in Immune Cells.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  18. Article
  19. Murine Alox8 versus the human ALOX15B ortholog: differences and similarities.Pflugers Archiv : European journal of physiology · 2024
    Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 2 institutions in 2 countries.

Quan D ZhouDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-0184-4884
Xun ChiDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-5519-6037
Min Sub LeeDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Wei Yuan HsiehDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Jonathan J MkrtchyanDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
An-Chieh FengDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Cuiwen HeDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Autumn G YorkDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Viet L BuiDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Eliza B KronenbergerDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Alessandra FerrariDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Xu XiaoDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Allison E DalyDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-7030-8663
Elizabeth J TarlingDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-0599-0432
Robert DamoiseauxDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Philip O ScumpiaDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Stephen T SmaleDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Kevin J WilliamsDepartment of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA.
Peter TontonozDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-1259-0477
Steven J BensingerDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA. sbensinger@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-9657-4206
University of California, Los Angeles · USHoward Hughes Medical Institute · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Understanding the Influence of Lipid Homeostasis on T cell FunctionP01HL146358 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FONG, LOREN GI · 2019 to 2023
$11.7M
MULTIDISCIPLINARY TRAINING IN MICROBIAL PATHOGENESIST32AI007323 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peter John Bradley · 1988 to 2026
$8.6M
Post-Translational Regulation of Lipid MetabolismR01HL136543 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TARLING, ELIZABETH JOANNA · 2017 to 2021
$1.9M
Understanding the influence of SREBP signaling on CD4 T helper cell biologyR01AI122282 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BENSINGER, STEVEN J · 2016 to 2020
$1.9M
Determining the Impact of SREBP on Adaptive ImmunityR01AI093768 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BENSINGER, STEVEN J · 2012 to 2015
$1.5M
Cytosolic DNA sensors in cutaneous wound healing and host defenseR03AR073940 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SCUMPIA, PHILIP · 2018 to 2019
$156k
Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR001881NHLBI NIH HHS P01 HL146358NHLBI NIH HHS R01 HL136543NIAID NIH HHS R01 AI093768NIAID NIH HHS R01 AI122282NIAID NIH HHS T32 AI007323NIAMS NIH HHS R03 AR073940
6 · The paper itself

Abstract

Plasma membranes of animal cells are enriched for cholesterol. Cholesterol-dependent cytolysins (CDCs) are pore-forming toxins secreted by bacteria that target membrane cholesterol for their effector function. Phagocytes are essential for clearance of CDC-producing bacteria; however, the mechanisms by which these cells evade the deleterious effects of CDCs are largely unknown. Here, we report that interferon (IFN) signals convey resistance to CDC-induced pores on macrophages and neutrophils. We traced IFN-mediated resistance to CDCs to the rapid modulation of a specific pool of cholesterol in the plasma membrane of macrophages without changes to total cholesterol levels. Resistance to CDC-induced pore formation requires the production of the oxysterol 25-hydroxycholesterol (25HC), inhibition of cholesterol synthesis and redistribution of cholesterol to an esterified cholesterol pool. Accordingly, blocking the ability of IFN to reprogram cholesterol metabolism abrogates cellular protection and renders mice more susceptible to CDC-induced tissue damage. These studies illuminate targeted regulation of membrane cholesterol content as a host defense strategy.

Indexed as

AnimalsBacteriaBacterial InfectionsBacterial ProteinsBacterial ToxinsCell MembraneCell Membrane PermeabilityCells, CulturedDisease Models, AnimalDisease SusceptibilityFemaleHost Microbial InteractionsHumansHydroxycholesterolsInterferonsIntravital Microscopy25-hydroxycholesterolBacterial ProteinsBacterial Toxinscholesterol 25-hydroxylaseHydroxycholesterolsInterferonsSteroid Hydroxylasesstreptolysin OStreptolysins

Identifiers

PMID32514064
PMCPMC7778040
OpenAlexW3033750705

What OpenQuestion holds

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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.