NHR-49 transcription factor regulates immunometabolic response and survival of caenorhabditis elegans during enterococcus faecalis infection

Madhumanti Dasgupta, Meghana Shashikanth, Anjali Gupta, Anjali Sandhu, Atreyee De, Salil Javed, Varsha Singh (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)
12 Downloads (Pure)

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 proliferatoractivated 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.

Original languageEnglish
Article numbere00130-20
JournalInfection and Immunity
Volume88
Issue number8
Early online date1 Jun 2020
DOIs
Publication statusPublished - 21 Jul 2020

Keywords

  • Caenorhabditis elegans
  • Cryptococcus neoformans
  • Enterococcus faecalis
  • Fatty acids
  • Immune response
  • Metabolism
  • Nuclear hormone receptor
  • Nutritional immunity
  • Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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