Abstract
Immune response to pathogens is energetically expensive to the host; however, the cellular source of energy to fuel immune response remains unknown. In this study, we show that Caenorhabditis elegans exposed to pathogenic Gram-positive and Gram-negative bacteria or yeast rapidly utilizes lipid droplets, the major energy reserve. The nematode's response to the pathogenic bacterium Enterococcus faecalis entails metabolic rewiring for the upregulation of several genes involved in lipid utilization and downregulation of lipid synthesis genes. Genes encoding acyl-CoA synthetase ACS-2, involved in lipid metabolism, and flavin monooxygenase FMO-2, involved in detoxification, are two highly upregulated genes during E. faecalis infection. We find that both ACS-2 and FMO-2 are necessary for survival and rely on NHR-49, a peroxisome proliferator-activated receptor alpha (PPARα) ortholog, for upregulation during E. faecalis infection. Thus, NHR-49 regulates an immunometabolic axis of survival in C. elegans by modulating breakdown of lipids as well as immune effector production upon E. faecalis exposure.
Highlights
Immune response to pathogens is energetically expensive to the host; the cellular source of energy to fuel immune response remains unknown
To find evidence of energy utilization by the host during infection, we characterized the transcriptional response of C. elegans to different pathogens, E. faecalis OG1RF, P. aeruginosa PA14, and C. neoformans H99, by RNA sequencing
During OG1RF infection, 57 immune effectors and 75 metabolic genes were upregulated, while 35 immune effectors and 60 metabolic genes were upregulated during H99 infection, suggesting that transcripts for metabolic genes represented an appreciable proportion of C. elegans response at 8 h of infection
Summary
Immune response to pathogens is energetically expensive to the host; the cellular source of energy to fuel immune response remains unknown. RESULTS Exposure of C. elegans to pathogens induces transcriptional upregulation of lipid breakdown pathways and immune effectors. To find evidence of energy utilization by the host during infection, we characterized the transcriptional response of C. elegans to different pathogens, E. faecalis OG1RF, P. aeruginosa PA14, and C. neoformans H99, by RNA sequencing.
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