Type

Other / n/a

Authors

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

Subjects

Microbiology

Topics
cytotoxicity phagocytosis lactic acid animals cytotoxicity immunologic macrophages mycobacterium tuberculosis pharmacy and pharmaceutical sciences nf kappa b polyglycolic acid cell line cell death mice autophagy cytokines caspases immunologic humans

Treatment of Mycobacterium tuberculosis-Infected Macrophages with Poly(Lactic-Co-Glycolic Acid) Microparticles Drives NFκB and Autophagy Dependent Bacillary Killing. (2016)

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.
Collections Ireland -> Royal College of Surgeons in Ireland -> School of Pharmacy
Ireland -> Royal College of Surgeons in Ireland -> School of Pharmacy Articles

Full list of authors on original publication

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

Experts in our system

1
Mary P O'Sullivan
Trinity College Dublin
Total Publications: 19
 
2
Joseph Keane
Trinity College Dublin
Total Publications: 54
 
3
Sally-Ann Cryan
Royal College of Surgeons in Ireland
Total Publications: 70
 
4
Paul J Gallagher
Royal College of Surgeons in Ireland
 
5
Seonadh O'Leary
Trinity College Dublin
Total Publications: 12
 
6
Gemma O'Connor
Royal College of Surgeons in Ireland
Total Publications: 5
 
7
Ciaran Lawlor
Royal College of Surgeons in Ireland
Total Publications: 8