Immune-metabolic response of Caenorhabditis elegans to Enterococcus faecalis
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Immune response to pathogens is energetically expensive to the host. In this study, we show that Caenorhabditis elegans exposed for 8 hours to pathogenic Gram-positive bacteria, Enterococcus faecalis and Staphylococcus aureus, and pathogenic yeast, Cryptococcus neoformans, undergoes complete breakdown of lipid droplets (LDs) which are the major energy reserves in the nematode. We also show that C. elegans fed on pathogenic Gram-negative bacteria, Pseudomonas aeruginosa and Salmonella typhimurium, undergoes a slower rate of LD breakdown, with depletion beginning only around 12-24 hours. Our study, suggests that rapid LD hydrolysis by E. faecalis diet is due to nutritional stress and not due to the presence of toxins. E. faecalis diet causes defects in growth, carbohydrate levels, and brood size in adult C. elegans and developmental arrest in larval animals. In agreement to the early LD depletion, we also find that E. faecalis diet, similar to starvation stress, causes a transcriptional response resulting in dis-homeostasis in the expression of lipid metabolic genes. We report the induction of lipases, beta-oxidation enzymes, glyoxylate pathway, and gluconeogenesis in E. faecalis-fed animals. There is also a concomitant decrease in the expression of genes involved in lipid synthesis. Similar genes are dysregulated even in starved animals. We find that LD utilization appears to be a protective response, and C. elegans survival on E. faecalis can be boosted by an increase in lipid stores via dietary or genetic manipulation. Additionally, we find that NHR-49, the homolog of mammalian PPARα, regulates the immune-metabolic axis of survival in C. elegans by modulating breakdown of lipids as well as immune effector production upon E. faecalis exposure. Our findings reveal a facet of nutritional immunity wherein lipid droplet homeostasis plays a central role in governing nematode-microbe interactions.