NHR-49/PAARα and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase
AuthorsWani, Khursheed A.
UMass Chan AffiliationsDepartment of Microbiology and Physiological Systems
transcriptional defense responses
Bacterial Infections and Mycoses
Immunology and Infectious Disease
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AbstractDuring bacterial infection, the host is confronted with multiple overlapping signals that are integrated at the organismal level to produce defensive host responses. How multiple signals are sensed by the host and how they elicit the transcription of specific host defense genes is much less understood at the whole-animal level than at the cellular level. The model organism Caenorhabditis elegans is known to mount transcriptional defense responses against intestinal bacterial infections that elicit overlapping starvation and infection responses, but the specific regulation of such responses is not well understood. By directly comparing C. elegans that were either starved or infected with Gram-positive bacterium Staphylococcus aureus revealed a large infection-specific transcriptional signature. This signature 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. We found that the mechanism of fmo-2/FMO5 induction required the nuclear hormone receptor, NHR-49/PPARa, which induced fmo-2/FMO5 and host defense cell non-autonomously. Moreover, deletion of fmo-2/FMO5 severely compromised infection survival, thus identifying the first FMO important for innate immunity in animals. These findings for the first time reveal an infection-specific host response to S. aureus, identify HLH-30/TFEB as its main regulator, reveal that NHR-49/PPARa contributes to host defense, and demonstrate that FMOs are important innate immunity effectors in animals.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/46445
Presented virtually during the "Post-Doc Talks" session at the 25th Annual University of Massachusetts Medical School Research Retreat 2020 on October 26, 2020.
RightsCopyright © 2020 Wani. This is an open access document distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright © 2020 Wani. This is an open access document distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.