UMMS Affiliation

Department of Microbiology and Physiological Systems; Graduate School of Biomedical Sciences

Publication Date

2021-05-12

Document Type

Article

Disciplines

Bacterial Infections and Mycoses | Immunology of Infectious Disease | Immunopathology

Abstract

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.

Keywords

C. elegans, S. aureus, host defense, immunology, inflammation, intestine, transcription factors

Rights and Permissions

Copyright © 2021, Wani et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

DOI of Published Version

10.7554/eLife.62775

Source

Wani KA, Goswamy D, Taubert S, Ratnappan R, Ghazi A, Irazoqui JE. NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase. Elife. 2021 May 12;10:e62775. doi: 10.7554/eLife.62775. PMID: 33978570; PMCID: PMC8139828. Link to article on publisher's site

Journal/Book/Conference Title

eLife

Related Resources

Link to Article in PubMed

PubMed ID

33978570

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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