Abstract
Tuberculosis (TB) is the world's biggest infectious disease killer. The increasing prevalence of multidrug-resistant and extensively drug-resistant TB demonstrates that current treatments are inadequate and there is an urgent need for novel therapies. Research is now focused on the development of host-directed therapies (HDTs) which can be used in combination with existing antimicrobials, with a special focus on promoting host defense. Immunometabolic reprogramming is integral to TB host defense, therefore, understanding and supporting the immunometabolic pathways that are altered after infection will be important for the development of new HDTs. Moreover, TB pathophysiology is interconnected with iron metabolism. Iron is essential for the survival of Mycobacterium tuberculosis (Mtb), the bacteria that causes TB disease. Mtb struggles to replicate and persist in low iron environments. Iron chelation has therefore been suggested as a HDT. In addition to its direct effects on iron availability, iron chelators modulate immunometabolism through the stabilization of HIF1α. This review examines immunometabolism in the context of Mtb and its links to iron metabolism. We suggest that iron chelation, and subsequent stabilization of HIF1α, will have multifaceted effects on immunometabolic function and holds potential to be utilized as a HDT to boost the host immune response to Mtb infection.
Highlights
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis (Mtb) and it is estimated that just under one quarter of the global population may be latently infected with Mtb [1, 2]
We present the evidence suggesting that iron chelation, and its effects on immunometabolism, may be a plausible adjunctive host-directed therapies (HDTs) option for TB
This switch to glycolysis occurs in immune cells that are activated by pro-inflammatory signals, which differ depending on the cell type, and allows them to produce adenosine triphosphate (ATP) more rapidly and provides the necessary metabolic intermediates needed for cell growth, proliferation and effector mechanisms [23]
Summary
Reviewed by: Adrie J.C. Steyn, University of Alabama at Birmingham, United States Bruno Bezerril Andrade, Fundação Oswaldo Cruz (Fiocruz), Brazil. Specialty section: This article was submitted to Molecular Innate Immunity, a section of the journal
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