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

TY - JOUR

T1 - NHR-49 transcription factor regulates immunometabolic response and survival of caenorhabditis elegans during enterococcus faecalis infection

AU - Dasgupta, Madhumanti

AU - Shashikanth, Meghana

AU - Gupta, Anjali

AU - Sandhu, Anjali

AU - De, Atreyee

AU - Javed, Salil

AU - Singh, Varsha

N1 - Publisher Copyright: Copyright © 2020 Dasgupta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

PY - 2020/7/21

Y1 - 2020/7/21

N2 - 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.

AB - 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.

KW - Caenorhabditis elegans

KW - Cryptococcus neoformans

KW - Enterococcus faecalis

KW - Fatty acids

KW - Immune response

KW - Metabolism

KW - Nuclear hormone receptor

KW - Nutritional immunity

KW - Pseudomonas aeruginosa

UR - https://www.scopus.com/pages/publications/85088606855

U2 - 10.1128/IAI.00130-20

DO - 10.1128/IAI.00130-20

M3 - Article

C2 - 32482643

AN - SCOPUS:85088606855

SN - 0019-9567

VL - 88

JO - Infection and Immunity

JF - Infection and Immunity

IS - 8

M1 - e00130-20

ER -