Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine; Department of Molecular, Cell and Cancer Biology
Amino Acids, Peptides, and Proteins | Bacterial Infections and Mycoses | Biochemical Phenomena, Metabolism, and Nutrition | Genetic Phenomena | Hemic and Immune Systems | Immunology and Infectious Disease | Lipids | Microbial Physiology | Pathogenic Microbiology
Early host responses toward pathogens are essential for defense against infection. In Caenorhabditis elegans, the transcription factor, SKN-1, regulates cellular defenses during xenobiotic intoxication and bacterial infection. However, constitutive activation of SKN-1 results in pleiotropic outcomes, including a redistribution of somatic lipids to the germline, which impairs health and shortens lifespan. Here, we show that exposing C. elegans to Pseudomonas aeruginosa similarly drives the rapid depletion of somatic, but not germline, lipid stores. Modulating the epigenetic landscape refines SKN-1 activity away from innate immunity targets, which alleviates negative metabolic outcomes. Similarly, exposure to oxidative stress redirects SKN-1 activity away from pathogen response genes while restoring somatic lipid distribution. In addition, activating p38/MAPK signaling in the absence of pathogens, is sufficient to drive SKN-1-dependent loss of somatic fat. These data define a SKN-1- and p38-dependent axis for coordinating pathogen responses, lipid homeostasis, and survival and identify transcriptional redirection, rather than inactivation, as a mechanism for counteracting the pleiotropic consequences of aberrant transcriptional activity.
C. elegans, H3K4me3, SKN-1, lipid metabolism, pathogen
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Copyright © 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
DOI of Published Version
Proc Natl Acad Sci U S A. 2019 Oct 29;116(44):22322-22330. doi: 10.1073/pnas.1909666116. Epub 2019 Oct 14. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Nhan JD, Turner CD, Anderson SM, Yen C, Dalton HM, Cheesman HK, Ruter DL, Uma Naresh N, Haynes CM, Soukas AA, Pukkila-Worley R, Curran SP. (2019). Redirection of SKN-1 abates the negative metabolic outcomes of a perceived pathogen infection. Open Access Publications by UMass Chan Authors. https://doi.org/10.1073/pnas.1909666116. Retrieved from https://escholarship.umassmed.edu/oapubs/4028
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Amino Acids, Peptides, and Proteins Commons, Bacterial Infections and Mycoses Commons, Biochemical Phenomena, Metabolism, and Nutrition Commons, Genetic Phenomena Commons, Hemic and Immune Systems Commons, Immunology and Infectious Disease Commons, Lipids Commons, Microbial Physiology Commons, Pathogenic Microbiology Commons