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

eLife, 2021-05, Vol.10 [Peer Reviewed Journal]

COPYRIGHT 2021 eLife Science Publications, Ltd. ;ISSN: 2050-084X ;EISSN: 2050-084X ;DOI: 10.7554/eLife.62775

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  • Title:
    NHR-49/PPAR-[alpha] and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase
  • Author: Wani, Khursheed A ; Goswamy, Debanjan ; Taubert, Stefan ; Ratnappan, Ramesh ; Ghazi, Arjumand ; Irazoqui, Javier E
  • Subjects: Genetic transcription ; Health aspects ; Infection ; Medical research ; Medicine, Experimental ; Staphylococcal infections ; Staphylococcus aureus
  • Is Part Of: eLife, 2021-05, Vol.10
  • Description: 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-[alpha], 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-[alpha] during S. aureus infection, with implications for host defense and inflammation in higher organisms.
  • Publisher: eLife Science Publications, Ltd
  • Language: English
  • Identifier: ISSN: 2050-084X
    EISSN: 2050-084X
    DOI: 10.7554/eLife.62775
  • Source: TestCollectionTL3OpenAccess
    PubMed Central
    ROAD: Directory of Open Access Scholarly Resources
    ProQuest Central
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