Mycobacterium tuberculosis Limits Host Glycolysis and IL-1β by Restriction of PFK-M via MicroRNA-21
Autor: | Hugo Charles-Messance, Anna Wedderburn, Emer E. Hackett, Ed C. Lavelle, Mireille Ouimet, Joseph Keane, Natalia Muñoz-Wolf, Laura E. Gleeson, Frederick J. Sheedy, Seónadh O'Leary, Kathryn J. Moore, Daniel G.W. Johnston, Michelle A. Williams, Sinéad C. Corr, Sarah Case, Stephen V. Gordon, Alicia Smyth |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Phosphofructokinase-1 Interleukin-1beta Anti-Inflammatory Agents Article General Biochemistry Genetics and Molecular Biology Mycobacterium tuberculosis Interferon-gamma Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Interferon medicine Animals Humans Tuberculosis Macrophage Glycolysis Interferon gamma Psychological repression lcsh:QH301-705.5 Cell Proliferation Base Sequence biology Macrophages Macrophage Activation biology.organism_classification 3. Good health Cell biology MicroRNAs HEK293 Cells RAW 264.7 Cells 030104 developmental biology lcsh:Biology (General) Host-Pathogen Interactions 030217 neurology & neurosurgery medicine.drug Phosphofructokinase |
Zdroj: | Cell Reports, Vol 30, Iss 1, Pp 124-136.e4 (2020) Cell Rep |
ISSN: | 2211-1247 |
Popis: | Summary: 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. : Hackett et al. identify a role for the anti-inflammatory miR-21 in limiting host glycolysis during tuberculosis (TB) infection to favor bacterial replication. This occurs by targeting a pro-glycolytic isoform at the rate-limiting step in glycolysis, PFK-M, a process antagonized by the host Th1-cytokine IFN-γ, to promote full macrophage activation and antimicrobial function. Keywords: macrophage, metabolic reprogramming, tuberculosis, mycobacterium tuberculosis, glycolysis, microRNA, miR-21, interleukin-1b, phosphofructokinase, interferon gamma |
Databáze: | OpenAIRE |
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