Temporal modulation of host aerobic glycolysis determines the outcome of Mycobacterium marinum infection

Publication date: Available online 24 November 2019Source: Fish & Shellfish ImmunologyAuthor(s): Yuanqing Kan, Lu Meng, Lingling Xie, Lixia Liu, Wenyue Dong, Jintao Feng, Yuchen Yan, Chao Zhao, Gang Peng, Decheng Wang, Mingfang Lu, Chen Yang, Chen NiuAbstractMacrophages are the first-line host defense that the invading Mycobacterium tuberculosis (Mtb) encounters. It has been recently reported that host aerobic glycolysis was elevated post the infection by a couple of virulent mycobacterial species. However, whether this metabolic transition is required for host defense against intracellular pathogens and the underlying mechanisms remain to be further investigated. A pathogenic mycobacterial species, M. marinum, is genetic close to Mtb and was utilized in this study. Through analyzing cellular carbon metabolism of RAW 264.7 (a murine macrophage-like cell line) post M. marinum infection, a strong elevation of glycolysis was observed. Next, three glycolysis inhibitors were examined for their ability to inhibit mycobacterial proliferation inside RAW264.7 macrophages. Among them, a glucose analog, 2-deoxyglucose (2-DG) displayed a protective role against mycobacterial infection. Treatment with 2-DG at concentrations of 0.5 or 1 mM significantly induced autophagy and decreased the phagocytosis of M. marinum by macrophages. Moreover, 2-DG pre-treatment exerted a significant protective effect on zebrafish larvae by limiting the proliferation of M. marinum, and such effect was corre...
Source: Fish and Shellfish Immunology - Category: Biology Source Type: research