Department of Microbiology and Physiological Systems; Graduate School of Biomedical Sciences
Bacterial Infections and Mycoses | Immunology of Infectious Disease | Immunopathology
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.
C. elegans, S. aureus, host defense, immunology, inflammation, intestine, transcription factors
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DOI of Published Version
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
Wani KA, Goswamy D, Taubert S, Ratnappan R, Ghazi A, Irazoqui JE. (2021). NHR-49/PPAR-alpha and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase. Open Access Publications by UMass Chan Authors. https://doi.org/10.7554/eLife.62775. Retrieved from https://escholarship.umassmed.edu/oapubs/4725
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