NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase
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 St...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/62775 |
| _version_ | 1828195743916097536 |
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| author | Khursheed A Wani Debanjan Goswamy Stefan Taubert Ramesh Ratnappan Arjumand Ghazi Javier E Irazoqui |
| author_facet | Khursheed A Wani Debanjan Goswamy Stefan Taubert Ramesh Ratnappan Arjumand Ghazi Javier E Irazoqui |
| author_sort | Khursheed A Wani |
| collection | DOAJ |
| 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-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. |
| first_indexed | 2024-04-12T09:47:12Z |
| format | Article |
| id | doaj.art-03c71d72b3f440ee89b5c14c2ba4609d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:47:12Z |
| publishDate | 2021-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-03c71d72b3f440ee89b5c14c2ba4609d2022-12-22T03:37:54ZengeLife Sciences Publications LtdeLife2050-084X2021-05-011010.7554/eLife.62775NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenaseKhursheed A Wani0https://orcid.org/0000-0003-3559-7962Debanjan Goswamy1Stefan Taubert2https://orcid.org/0000-0002-2432-7257Ramesh Ratnappan3https://orcid.org/0000-0001-7055-9043Arjumand Ghazi4https://orcid.org/0000-0002-5859-4206Javier E Irazoqui5https://orcid.org/0000-0001-6553-1329Department of Microbiology and Physiological Systems, UMass Medical School, Worcester, United StatesDepartment of Microbiology and Physiological Systems, UMass Medical School, Worcester, United StatesDepartment of Medical Genetics, University of British Columbia, Vancouver, CanadaDepartment 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 StatesDepartment 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 StatesDepartment of Microbiology and Physiological Systems, UMass Medical School, Worcester, United StatesThe 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.https://elifesciences.org/articles/62775intestinetranscription factorshost defense |
| spellingShingle | Khursheed A Wani Debanjan Goswamy Stefan Taubert Ramesh Ratnappan Arjumand Ghazi Javier E Irazoqui NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase eLife intestine transcription factors host defense |
| title | NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase |
| title_full | NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase |
| title_fullStr | NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase |
| title_full_unstemmed | NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase |
| title_short | NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase |
| title_sort | nhr 49 ppar α and hlh 30 tfeb cooperate for c elegans host defense via a flavin containing monooxygenase |
| topic | intestine transcription factors host defense |
| url | https://elifesciences.org/articles/62775 |
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