Journal article
Desferrioxamine Supports Metabolic Function in Primary Human Macrophages Infected With Mycobacterium tuberculosis
Frontiers in immunology, Vol.11, pp.836-836
05/13/2020
DOI: 10.3389/fimmu.2020.00836
PMCID: PMC7237728
PMID: 32477344
Abstract
Tuberculosis is the single biggest infectious killer in the world and presents a major global health challenge. Antimicrobial therapy requires many months of multiple drugs and incidences of drug resistant tuberculosis continues to rise. Consequently, research is now focused on the development of therapies to support the function of infected immune cells. HIF1 alpha-mediated induction of aerobic glycolysis is integral to the host macrophage response during infection with Mtb, as this promotes bacillary clearance. Some iron chelators have been shown to modulate cellular metabolism through the regulation of HIF1 alpha. We examined if the iron chelator, desferrioxamine (DFX), could support the function of primary human macrophages infected with Mtb. Using RT-PCR, we found that DFX promoted the expression of key glycolytic enzymes in Mtb-infected primary human MDMs and human alveolar macrophages. Using Seahorse technology, we demonstrate that DFX enhances glycolytic metabolism in Mtb-stimulated human MDMs, while helping to enhance glycolysis during mitochondrial distress. Furthermore, the effect of DFX on glycolysis was not limited to Mtb infection as DFX also boosted glycolytic metabolism in uninfected and LPS-stimulated cells. DFX also supports innate immune function by inducing IL1 beta production in human macrophages during early infection with Mtb and upon stimulation with LPS. Moreover, using hypoxia, Western blot and ChIP-qPCR analyses, we show that DFX modulates IL1 beta levels in these cells in a HIF1 alpha-mediated manner. Collectively, our data suggests that DFX exhibits potential to enhance immunometabolic responses and augment host immune function during early Mtb infection, in selected clinical settings.
Details
- Title: Subtitle
- Desferrioxamine Supports Metabolic Function in Primary Human Macrophages Infected With Mycobacterium tuberculosis
- Creators
- James Joseph Phelan - Trinity College DublinKate McQuaid - Trinity College DublinColin Kenny - National Children’s Research CentreKarl Michael Gogan - Trinity College DublinDonal J. Cox - Trinity College DublinSharee Ann Basdeo - Trinity College DublinSeonadh O'Leary - Trinity College DublinSimone Christa Tazoll - Trinity College DublinCilian O. Maoldomhnaigh - Trinity College DublinMary P. O'Sullivan - Trinity College DublinLuke A. O'Neill - Trinity College DublinMaureen J. O'Sullivan - National Children’s Research CentreJoseph Keane - Trinity College Dublin
- Resource Type
- Journal article
- Publication Details
- Frontiers in immunology, Vol.11, pp.836-836
- DOI
- 10.3389/fimmu.2020.00836
- PMID
- 32477344
- PMCID
- PMC7237728
- NLM abbreviation
- Front Immunol
- ISSN
- 1664-3224
- eISSN
- 1664-3224
- Publisher
- Frontiers Media Sa
- Number of pages
- 18
- Grant note
- Royal City of Dublin Hospital Trust (Baggot Street Hospital, Dublin, Ireland) 18/TIDA/6026 / Science Foundation Ireland; European Commission
- Language
- English
- Date published
- 05/13/2020
- Academic Unit
- Surgery
- Record Identifier
- 9984321860602771
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