NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase

eLife

Stefan Taubert¹  Debanjan Goswamy²  Javier E Irazoqui²  Khursheed A Wani²  Arjumand Ghazi³  Ramesh Ratnappan³ 

[1] Department of Medical Genetics, University of British Columbia, Vancouver, Canada;Department of Microbiology and Physiological Systems, UMass Medical School, Worcester, United States;Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, United States;Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States;Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States;Department of Physiology, University of Pittsburgh School of Medicine, Pittsburgh, United States;

关键词: intestine;    transcription factors;    host defense;    C. elegans;    S. aureus;   

DOI  :  10.7554/eLife.62775

来源: eLife Sciences Publications, Ltd

【 摘 要 】

The model organism Caenorhabditis elegans mounts transcriptional defense responses against intestinal bacterial infections that elicit overlapping starvation and infection responses, the regulation of which is not well understood. Direct comparison of C. elegans that were starved or infected with Staphylococcus aureus revealed a large infection-specific transcriptional signature, which was almost completely abrogated by deletion of transcription factor hlh-30/TFEB, except for six genes including a flavin-containing monooxygenase (FMO) gene, fmo-2/FMO5. Deletion of fmo-2/FMO5 severely compromised infection survival, thus identifying the first FMO with innate immunity functions in animals. Moreover, fmo-2/FMO5 induction required the nuclear hormone receptor, NHR-49/PPAR-α, which controlled host defense cell non-autonomously. These findings reveal an infection-specific host response to S. aureus, identify HLH-30/TFEB as its main regulator, reveal FMOs as important innate immunity effectors in animals, and identify the mechanism of FMO regulation through NHR-49/PPAR-α during S. aureus infection, with implications for host defense and inflammation in higher organisms.

【 授权许可】

CC BY