Evidence map›Paper›PMID 25090652›Full record

ArticlePloS one2014

HIV-derived ssRNA binds to TLR8 to induce inflammation-driven macrophage foam cell formation.

Mark A Bernard, Xinbing Han, Sonya Inderbitzin, Ifunanya Agbim, Hui Zhao, Henry Koziel, Souvenir D Tachado

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

19 citing papers in PubMed, 31 citations in OpenAlex.

  1. Trial
  2. miR-574-5p in epigenetic regulation and Toll-like receptor signaling.Cell communication and signaling : CCS · 2024
    Review
  3. Review
  4. Review
  5. The Relevance of TLR8 in Viral Infections.Pathogens (Basel, Switzerland) · 2022
    Review
  6. Review
  7. Article
  8. Betamethasone induces potent immunosuppression and reduces HIV infection in a PBMC in vitro model.Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2021
    Article
  9. Review
  10. Review
  11. Foam Cells: One Size Doesn't Fit All.Trends in immunology · 2019
    Review
  12. Review
  13. Article
  14. Review
  15. HIV-1-Associated Atherosclerosis: Unraveling the Missing Link.Journal of the American College of Cardiology · 2017
    Review
  16. Article
  17. Review
  18. Article
  19. Article
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 4 institutions in 2 countries.

Mark A BernardDivision of Pulmonary, Critical Care, and Sleep Medicine; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.
Xinbing HanDivision of Pulmonary, Critical Care, and Sleep Medicine; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.
Sonya InderbitzinDivision of Pulmonary, Critical Care, and Sleep Medicine; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.
Ifunanya AgbimDivision of Pulmonary, Critical Care, and Sleep Medicine; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.
Hui ZhaoDivision of Pulmonary, Critical Care, and Sleep Medicine; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America; From Department of Respiratory Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, PR China.
Henry KozielDivision of Pulmonary, Critical Care, and Sleep Medicine; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.
Souvenir D TachadoDivision of Pulmonary, Critical Care, and Sleep Medicine; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.
Beth Israel Deaconess Medical Center · USPulmonary and Critical Care Associates · USSleepMed · USHarvard University · US

Funding

HIV Compromises Lung Macrophage TLR Host Defense FunctionR01HL092811 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI TACHADO, SOUVENIR D · 2009 to 2013
$2.1M
NHLBI NIH HHS R01 HL092811NHLBI NIH HHS R01 HL92811PHS HHS NL 063655
6 · The paper itself

Abstract

Even though combined anti-retroviral therapy (cART) dramatically improves patient survival, they remain at a higher risk of being afflicted with non-infectious complications such as cardiovascular disease (CVD). This increased risk is linked to persistent inflammation and chronic immune activation. In this study, we assessed whether this complication is related to HIV-derived ssRNAs inducing in macrophages increases in TNFα release through TLR8 activation leading to foam cell formation. HIV ssRNAs induced foam cell formation in monocyte-derived macrophages (MDMs) in a dose-dependent manner. This response was reduced when either endocytosis or endosomal acidification was inhibited by dynasore or chloroquine, respectively. Using a flow cytometry FRET assay, we demonstrated that ssRNAs bind to TLR8 in HEK cells. In MDMs, ssRNAs triggered a TLR8-mediated inflammatory response that ultimately lead to foam cell formation. Targeted silencing of the TLR8 and MYD88 genes reduced foam cell formation. Furthermore, foam cell formation induced by these ssRNAs was blocked by an anti-TNFα neutralizing antibody. Taken together in MDMs, HIV ssRNAs are internalized; bind TLR8 in the endosome followed by endosomal acidification. TLR8 signaling then triggers TNFα release and ultimately leads to foam cell formation. As this response was inhibited by a blocking anti-TNFα antibody, drug targeting HIV ssRNA-driven TLR8 activation may serve as a potential therapeutic target to reduce chronic immune activation and inflammation leading to CVD in HIV+ patients.

Indexed as

Antibodies, NeutralizingBronchoalveolar Lavage FluidChloroquineEndocytosisEndosomesFoam CellsGene Expression RegulationHEK293 CellsHIVHumansHydrazonesHydrogen-Ion ConcentrationInflammationMacrophagesMacrophages, AlveolarMyeloid Differentiation Factor 88Antibodies, NeutralizingChloroquineHydrazonesMYD88 protein, humanMyeloid Differentiation Factor 88N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazideRNA, ViralTLR8 protein, humanToll-Like Receptor 8Tumor Necrosis Factor-alpha

Identifiers

PMID25090652
PMCPMC4121254
OpenAlexW2154433020

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.