Evidence map›Paper›PMID 26894562›Full record

ArticlePloS one2016

Treatment of Mycobacterium tuberculosis-Infected Macrophages with Poly(Lactic-Co-Glycolic Acid) Microparticles Drives NFκB and Autophagy Dependent Bacillary Killing.

Ciaran Lawlor, Gemma O'Connor, Seonadh O'Leary, Paul J Gallagher, Sally-Ann Cryan, Joseph Keane, Mary P O'Sullivan

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

22 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. AllCurrent research in immunology · 2022
    Review
  11. Article
  12. Article
  13. Article
  14. CD4mBio · 2020
    Article
  15. Experimental and therapeutic medicine · 2020
    Article
  16. Formulation of host-targeted therapeutics against bacterial infections.Translational research : the journal of laboratory and clinical medicine · 2020
    Review
  17. Review
  18. Article
  19. Single-dose Ag85B-ESAT6-loaded poly(lactic-International journal of nanomedicine · 2019
    Article
  20. 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 3 institutions in 1 country.

Ciaran LawlorSchool of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Gemma O'ConnorSchool of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Seonadh O'LearyDepartment of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, and St. James' Hospital, Dublin, Ireland.
Paul J GallagherSchool of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Sally-Ann CryanSchool of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Joseph KeaneDepartment of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, and St. James' Hospital, Dublin, Ireland.
Mary P O'SullivanDepartment of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, and St. James' Hospital, Dublin, Ireland.
Royal College of Surgeons in Ireland · IETrinity College Dublin · IESt. James's Hospital · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The emergence of multiple-drug-resistant tuberculosis (MDR-TB) has pushed our available repertoire of anti-TB therapies to the limit of effectiveness. This has increased the urgency to develop novel treatment modalities, and inhalable microparticle (MP) formulations are a promising option to target the site of infection. We have engineered poly(lactic-co-glycolic acid) (PLGA) MPs which can carry a payload of anti-TB agents, and are successfully taken up by human alveolar macrophages. Even without a drug cargo, MPs can be potent immunogens; yet little is known about how they influence macrophage function in the setting of Mycobacterium tuberculosis (Mtb) infection. To address this issue we infected THP-1 macrophages with Mtb H37Ra or H37Rv and treated with MPs. In controlled experiments we saw a reproducible reduction in bacillary viability when THP-1 macrophages were treated with drug-free MPs. NFκB activity was increased in MP-treated macrophages, although cytokine secretion was unaltered. Confocal microscopy of immortalized murine bone marrow-derived macrophages expressing GFP-tagged LC3 demonstrated induction of autophagy. Inhibition of caspases did not influence the MP-induced restriction of bacillary growth, however, blockade of NFκB or autophagy with pharmacological inhibitors reversed this MP effect on macrophage function. These data support harnessing inhaled PLGA MP-drug delivery systems as an immunotherapeutic in addition to serving as a vehicle for targeted drug delivery. Such "added value" could be exploited in the generation of inhaled vaccines as well as inhaled MDR-TB therapeutics when used as an adjunct to existing treatments.

Indexed as

AnimalsAutophagyCaspasesCell DeathCell LineCytokinesCytotoxicity, ImmunologicHumansLactic AcidMacrophagesMiceMycobacterium tuberculosisNF-kappa BPhagocytosisPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerCaspasesCytokinesLactic AcidNF-kappa BPolyglycolic AcidPolylactic Acid-Polyglycolic Acid Copolymer

Identifiers

PMID26894562
PMCPMC4760758
OpenAlexW2287273668

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.