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. 2024 Oct;598(20):2592-2614.
doi: 10.1002/1873-3468.15001. Epub 2024 Aug 18.

The miR-26a/SIRT6/HIF-1α axis regulates glycolysis and inflammatory responses in host macrophages during Mycobacterium tuberculosis infection

Soumya Mal  1 , Debayan Majumder  2 , Pankaj Birari  2 , Arun Kumar Sharma  2 , Umesh Gupta  3 , Kuladip Jana  1 , Manikuntala Kundu  2 , Joyoti Basu  2
Affiliations
Free article

The miR-26a/SIRT6/HIF-1α axis regulates glycolysis and inflammatory responses in host macrophages during Mycobacterium tuberculosis infection

Soumya Mal et al. FEBS Lett. 2024 Oct.
Free article

Abstract

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis. Here, a macrophage infection model was used to unravel the role of the histone deacetylase sirtuin 6 (SIRT6) in Mtb-triggered regulation of the innate immune response. Mtb infection downregulated microRNA-26a and upregulated its target SIRT6. SIRT6 suppressed glycolysis and expression of HIF-1α-dependent glycolytic genes during infection. In addition, SIRT6 regulated the levels of intracellular succinate which controls stabilization of HIF-1α, as well as the release of interleukin (IL)-1β. Furthermore, SIRT6 inhibited inducible nitric oxide synthase (iNOS) and proinflammatory IL-6 but augmented anti-inflammatory arginase expression. The miR-26a/SIRT6/HIF-1α axis therefore regulates glycolysis and macrophage immune responses during Mtb infection. Our findings link SIRT6 to rewiring of macrophage signaling pathways facilitating dampening of the antibacterial immune response.

Keywords: Mycobacterium tuberculosis; glycolysis; immunometabolism; innate immunity; macrophage response; sirtuin 6.

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References

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