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dc.contributor.authorNhan, James D.
dc.contributor.authorTurner, Christian D.
dc.contributor.authorAnderson, Sarah M.
dc.contributor.authorYen, Chia-An
dc.contributor.authorDalton, Hans M.
dc.contributor.authorCheesman, Hilary K.
dc.contributor.authorRuter, Dana L.
dc.contributor.authorUma Naresh, Nandhitha
dc.contributor.authorHaynes, Cole M.
dc.contributor.authorSoukas, Alexander A.
dc.contributor.authorPukkila-Worley, Read
dc.contributor.authorCurran, Sean P.
dc.date2022-08-11T08:09:54.000
dc.date.accessioned2022-08-23T16:48:16Z
dc.date.available2022-08-23T16:48:16Z
dc.date.issued2019-10-29
dc.date.submitted2019-11-20
dc.identifier.citation<p>Proc Natl Acad Sci U S A. 2019 Oct 29;116(44):22322-22330. doi: 10.1073/pnas.1909666116. Epub 2019 Oct 14. <a href="https://doi.org/10.1073/pnas.1909666116">Link to article on publisher's site</a></p>
dc.identifier.issn0027-8424 (Linking)
dc.identifier.doi10.1073/pnas.1909666116
dc.identifier.pmid31611372
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41241
dc.description.abstractEarly 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31611372&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 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).
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectC. elegans
dc.subjectH3K4me3
dc.subjectSKN-1
dc.subjectlipid metabolism
dc.subjectpathogen
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBacterial Infections and Mycoses
dc.subjectBiochemical Phenomena, Metabolism, and Nutrition
dc.subjectGenetic Phenomena
dc.subjectHemic and Immune Systems
dc.subjectImmunology and Infectious Disease
dc.subjectLipids
dc.subjectMicrobial Physiology
dc.subjectPathogenic Microbiology
dc.titleRedirection of SKN-1 abates the negative metabolic outcomes of a perceived pathogen infection
dc.typeJournal Article
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume116
dc.source.issue44
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5046&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4028
dc.identifier.contextkey15830998
refterms.dateFOA2022-08-23T16:48:16Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/4028
dc.contributor.departmentDepartment of Molecular, Cell and Cancer Biology
dc.contributor.departmentProgram in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine
dc.source.pages22322-22330


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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).
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).