| First Author | Hackett EE | Year | 2020 |
| Journal | Cell Rep | Volume | 30 |
| Issue | 1 | Pages | 124-136.e4 |
| PubMed ID | 31914380 | Mgi Jnum | J:287554 |
| Mgi Id | MGI:6415432 | Doi | 10.1016/j.celrep.2019.12.015 |
| Citation | Hackett EE, et al. (2020) Mycobacterium tuberculosis Limits Host Glycolysis and IL-1beta by Restriction of PFK-M via MicroRNA-21. Cell Rep 30(1):124-136.e4 |
| abstractText | Increased glycolytic metabolism recently emerged as an essential process driving host defense against Mycobacterium tuberculosis (Mtb), but little is known about how this process is regulated during infection. Here, we observe repression of host glycolysis in Mtb-infected macrophages, which is dependent on sustained upregulation of anti-inflammatory microRNA-21 (miR-21) by proliferating mycobacteria. The dampening of glycolysis by miR-21 is mediated through targeting of phosphofructokinase muscle (PFK-M) isoform at the committed step of glycolysis, which facilitates bacterial growth by limiting pro-inflammatory mediators, chiefly interleukin-1beta (IL-1beta). Unlike other glycolytic genes, PFK-M expression and activity is repressed during Mtb infection through miR-21-mediated regulation, while other less-active isoenzymes dominate. Notably, interferon-gamma (IFN-gamma), which drives Mtb host defense, inhibits miR-21 expression, forcing an isoenzyme switch in the PFK complex, augmenting PFK-M expression and macrophage glycolysis. These findings place the targeting of PFK-M by miR-21 as a key node controlling macrophage immunometabolic function. |
