PUBLICATION
Temporal modulation of host aerobic glycolysis determines the outcome of Mycobacterium marinum infection
- Authors
- Kan, Y., Meng, L., Xie, L., Liu, L., Dong, W., Feng, J., Yan, Y., Zhao, C., Peng, G., Wang, D., Lu, M., Yang, C., Niu, C.
- ID
- ZDB-PUB-191128-10
- Date
- 2019
- Source
- Fish & shellfish immunology 96: 78-85 (Journal)
- Registered Authors
- Peng, Gang
- Keywords
- Glycolysis, Macrophages, Mycobacterium marinum, Phagocytosis, Zebrafish
- MeSH Terms
-
- Aerobiosis
- Animals
- Fish Diseases/metabolism*
- Fish Diseases/microbiology
- Glycolysis*
- Mice
- Mycobacterium Infections, Nontuberculous/metabolism
- Mycobacterium Infections, Nontuberculous/microbiology
- Mycobacterium Infections, Nontuberculous/veterinary*
- Mycobacterium marinum/physiology*
- RAW 264.7 Cells
- Zebrafish*
- PubMed
- 31775059 Full text @ Fish Shellfish Immunol.
Citation
Kan, Y., Meng, L., Xie, L., Liu, L., Dong, W., Feng, J., Yan, Y., Zhao, C., Peng, G., Wang, D., Lu, M., Yang, C., Niu, C. (2019) Temporal modulation of host aerobic glycolysis determines the outcome of Mycobacterium marinum infection. Fish & shellfish immunology. 96:78-85.
Abstract
Macrophages 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 correlated to tumor necrosis factor alpha (TNF-α) as the 2-DG pre-treatment increased the expression of TNF-α in both mouse peritoneal macrophages and zebrafish. On the contrary, the 2-DG treatment post infection did not restrain proliferation of M. marinum in WT zebrafish, and even accelerated bacterial replication in TNF-α-/- zebrafish. Together, modulation of glycolysis prior to infection boosts host immunity against M. marinum infection, indicating a potential intervention strategy to control mycobacterial infection.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping