Cited by 592Tuberculosis Research and EpidemiologyCell death mechanisms and regulationImmune Response and Inflammation

The DOI matches its Crossref record; 71 of the 72 references it cites were found in a registry or an index.

TNF Dually Mediates Resistance and Susceptibility to Mycobacteria via Mitochondrial Reactive Oxygen Species

Open access

Abstract

Tumor necrosis factor (TNF) constitutes a critical host defense against tuberculosis, but its excess is also implicated in tuberculosis pathogenesis in zebrafish and humans. Using the zebrafish, we elucidate the pathways by which TNF mediates tuberculosis pathogenesis. TNF excess induces mitochondrial reactive oxygen species (ROS) in infected macrophages through RIP1-RIP3-dependent pathways. While initially increasing macrophage microbicidal activity, ROS rapidly induce programmed necrosis (necroptosis) and release mycobacteria into the growth-permissive extracellular milieu. TNF-induced necroptosis occurs through two pathways: modulation of mitochondrial cyclophilin D, implicated in mitochondrial permeability transition pore formation, and acid sphingomyelinase-mediated ceramide production. Combined genetic blockade of cyclophilin D and acid sphingomyelinase renders the high TNF state hyperresistant by preventing macrophage necrosis while preserving increased microbicidal activity. Similarly, the cyclophilin D-inhibiting drug alisporivir and the acid sphingomyelinase-inactivating drug, desipramine, synergize to reverse susceptibility, suggesting the therapeutic potential of these orally active drugs against tuberculosis and possibly other TNF-mediated diseases.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cell.2013.03.022

Cites

71 of 71 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 72 references

1 of the 72 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Kim, 2010, NecroX as a novel class of mitochondrial reactive oxygen species and ONOO− scavenger, Arch. Pharm. Res., 33, 1813, 10.1007/s12272-010-1114-4 · DOI

Cited by

Sorted by citations

Items 501–592 of 592

Metadata

Authors
Roca, F. J., & Ramakrishnan, L.
Affiliations
University of Washington (US)
Corresponding author
Ramakrishnan, Lalita
Venue
Cell
Publisher
Elsevier BV
Published
2013-04
Volume
153
Issue
3
Pages
521-534
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2129443010
Cited by
592
References
72
Citations by year
2026: 26 · 2025: 38 · 2024: 47 · 2023: 32 · 2022: 45 · 2021: 54 · 2020: 59 · 2019: 36 · 2018: 37 · 2017: 43 · 2016: 45 · 2015: 48 · 2014: 60 · 2013: 22
FWCI
42.56
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Hispana (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (DP1OD006782)
  • National Institute of Allergy and Infectious Diseases (R01AI036396, R37AI054503)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
TNF-α, tuberculosis, mycobacteria, mitochondrial reactive oxygen species, necroptosis, cyclophilin D, mitochondrial permeability transition pore, acid sphingomyelinase, ceramide, macrophage microbicidal activity, alisporivir, desipramine, drug synergy, host-pathogen interaction, zebrafish model
MeSH terms
Peptidyl-Prolyl Isomerase F, Animals, Disease Models, Animal, Disease Susceptibility, Humans, Macrophages, Mitochondria, Mycobacterium, Necrosis, Tuberculosis, Zebrafish, Reactive Oxygen Species, Cyclophilins, Tumor Necrosis Factors, Receptor-Interacting Protein Serine-Threonine Kinases, Metabolic Networks and Pathways

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review