Redirection of SKN-1 abates the negative metabolic outcomes of a perceived pathogen infection
Authors
Nhan, James D.Turner, Christian D.
Anderson, Sarah M.
Yen, Chia-An
Dalton, Hans M.
Cheesman, Hilary K.
Ruter, Dana L.
Uma Naresh, Nandhitha
Haynes, Cole M.
Soukas, Alexander A.
Pukkila-Worley, Read
Curran, Sean P.
UMass Chan Affiliations
Department of Molecular, Cell and Cancer BiologyProgram in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine
Document Type
Journal ArticlePublication Date
2019-10-29Keywords
C. elegansH3K4me3
SKN-1
lipid metabolism
pathogen
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
Metadata
Show full item recordAbstract
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.Source
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
DOI
10.1073/pnas.1909666116Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41241PubMed ID
31611372Related Resources
Rights
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).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1073/pnas.1909666116
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Except where otherwise noted, this item's license is described as 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).