Abstract：
: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-1β (IL-1β). 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-γ (IFN-γ), 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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Hackett EE,Charles-Messance H,O'Leary SM,Gleeson LE,Muñoz-Wolf N,Case S,Wedderburn A,Johnston DGW,Williams MA,Smyth A,Ouimet M,Moore KJ,Lavelle EC,Corr SC,Gordon SV,Keane J,Sheedy FJdoi
10.1016/j.celrep.2019.12.015subject
Has Abstractpub_date
2020-01-07 00:00:00pages
124-136.e4issue
1issn
2211-1247pii
S2211-1247(19)31665-1journal_volume
30pub_type
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