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Redirection of SKN-1 abates the negative metabolic outcomes of a perceived pathogen infection.

ABSTRACT: 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.

SUBMITTER: Nhan JD

PROVIDER: S-EPMC6825279 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Redirection of SKN-1 abates the negative metabolic outcomes of a perceived pathogen infection.

Nhan James D JD Turner Christian D CD Anderson Sarah M SM Yen Chia-An CA Dalton Hans M HM Cheesman Hilary K HK Ruter Dana L DL Uma Naresh Nandhitha N Haynes Cole M CM Soukas Alexander A AA Pukkila-Worley Read R Curran Sean P SP

Proceedings of the National Academy of Sciences of the United States of America 20191014 44

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 simila ...[more]

PMID: 31611372

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Dataset Information

Redirection of SKN-1 abates the negative metabolic outcomes of a perceived pathogen infection.

Publications

Redirection of SKN-1 abates the negative metabolic outcomes of a perceived pathogen infection.

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