Dasgupta, Madhumanti et al. (2019) International Worm Meeting "Nuclear hormone receptor NHR-49 shapes immune-metabolic response of Caenorhabditis elegans to Enterococcus faecalis infection."

Singh, Varsha, Gupta, Anjali, Javed, Salil, Shashikanth, Meghana, Dasgupta, Madhumanti, Bojanala, Nagagireesh

[International Worm Meeting, 2019]

Immune responses to pathogenic microbes include activation of resistance and tolerance mechanisms in the host both of which are energetically expensive. In this study, we show that C. elegans fed on Gram positive bacterium, Enterococcus faecalis rapidly utilize lipid droplets, the major energy reserve in the nematode. Feeding on E. faecalis causes developmental arrest in C. elegans larvae and growth arrest in adults, compared to E. coli diet. We find that nematode's early response to infection entails an increase in expression of 10 genes involved in lipid breakdown as early as 8 hours of exposure, suggesting that neutral lipids are utilized as energy source during E. faecalis infection. Feeding on this pathogen also leads to a concomitant decrease in expression of lipid synthesis genes in C. elegans. We also show that lipid droplets play a protective role in C. elegans during infection. NHR-49, a PPAR? ortholog, is required for E. faecalis induced beta-oxidation of fatty acids and immune effector production and thus regulates an immuno-metabolic axis required for survival of the nematode on E. faecalis.