The Role Of Glycolysis For Innate Immunity In Caenorhabditis Elegans

The glycolysis metabolic pathway and the Tricarboxylic Acid (TCA) cyclearefundamentalmetabolic processes for providing energy and production of intermediate metabolites, which are ubiquitous and conserved in eukaryotes and heterotroph. Caenorhabditis elegans retains those pathways, participating in nutrition supplement and environmental adaption. C. eleganstightly controls those metabolized substrates through sophisticated mechanisms, such as allosteric regulation and substrate modification to extend the lifespan and regulate reproduction and development as well as maintainingmorphology and ability to response environmental changes. Mutation or deletion of those metabolic enzymes would influence development process and lifespan. In addition, metabolites could serve as signal molecules in biological processes, however, there is no current evidence for glycolysis and the tricarboxylic acid (TCA) cycle participate in nematodes innate immunity. We unutilized the strain of Pseudomonas aeruginosa PA14to infect C. elegans in order to build research model for further exploring the function of those metabolic enzymes in innate immunity. Firstly, we found that the hypoxia inducible factor HIF-1was up-regulated in infected nematodes, suggesting that PA14causes hypoxia stress. Secondly, we have screened the genes of relative enzymes which functioned in glycolysis metabolic pathway. After knockdown of the glycolytic rate limiting enzyme phosphofructokinase-1and pyruvate kinase, worms were more sensitive to PA14infection,suggesting that the glycolysis pathway is involved inin innate immunity of C. elegans. Furthermore, after PA14infection, the expression of phosphofructokinase-1and pyruvate kinase wasupregulated, which was dependent of HIF-1. Finally, we performedgene scanning onrelative enzyme in tricarboxylic acid cycle. The results showed that knockdown of enzymes in tricarboxylic acid cycle did not affect the resistance to PA14, suggesting that tricarboxylic acid cycle was not involved in innate immunity. In conclusion, our study has revealed thatPA14infection triggers nematodes hypoxia stress response, which in turn upregulatesthe expression of phosphofructokinase-1and pyruvate kinase. Both genes are involved in the resistance to PA14infection. Therefore, this study reveals a new nematode innate immune pathway in C. elegans.