Transcriptional suppression of sphingolipid catabolism controls pathogen resistance in C. elegans

被引：3

作者：

Nasrallah, Mohamad A. ^{[1
]}

Peterson, Nicholas D. ^{[1
]}

Szumel, Elizabeth S. ^{[1
]}

Liu, Pengpeng ^{[2
]}

Page, Amanda L. ^{[1
]}

Tse, Samantha Y. ^{[1
]}

Wani, Khursheed A. ^{[1
]}

Tocheny, Claire E. ^{[1
]}

Pukkila-Worley, Read ^{[1
]}

机构：

[1] Univ Massachusetts, Chan Med Sch, Dept Med, Program Innate Immun,Div Infect Dis & Immunol, Worcester, MA 01605 USA

[2] Univ Massachusetts, Chan Med Sch, Dept Mol Cell & Canc Biol, Worcester, MA USA

来源：

PLOS PATHOGENS | 2023年 / 19卷 / 10期

关键词：

CAENORHABDITIS-ELEGANS; NUCLEAR RECEPTORS; IMMUNE-RESPONSE; NEMATODE; METABOLISM; CERAMIDE; ROLES; SPHINGOSINE-1-PHOSPHATE; SPHINGOSINE; CONTRIBUTES;

D O I：

10.1371/journal.ppat.1011730

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Sphingolipids are required for diverse biological functions and are degraded by specific catabolic enzymes. However, the mechanisms that regulate sphingolipid catabolism are not known. Here we characterize a transcriptional axis that regulates sphingolipid breakdown to control resistance against bacterial infection. From an RNAi screen for transcriptional regulators of pathogen resistance in the nematode C. elegans, we identified the nuclear hormone receptor nhr-66, a ligand-gated transcription factor homologous to human hepatocyte nuclear factor 4. Tandem chromatin immunoprecipitation-sequencing and RNA sequencing experiments revealed that NHR-66 is a transcriptional repressor, which directly targets sphingolipid catabolism genes. Transcriptional de-repression of two sphingolipid catabolic enzymes in nhr-66 loss-of-function mutants drives the breakdown of sphingolipids, which enhances host susceptibility to infection with the bacterial pathogen Pseudomonas aeruginosa. These data define transcriptional control of sphingolipid catabolism in the regulation of cellular sphingolipids, a process that is necessary for pathogen resistance.

引用

页数：22

共 87 条

[1]

Abe A., 2013, Lipids Carbohydr Membr Membr Proteins: Artic Titles: S, P287, DOI DOI 10.1016/B978-0-12-378630-2.00462-X

[2] Genetic defects in the sphingolipid degradation pathway and their effects on microglia in neurodegenerative disease [J].