Program in Molecular Medicine
Cell Biology | Cellular and Molecular Physiology
Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we reveal that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans. These results demonstrate that autophagic pathways and autophagy are induced partly at the transcriptional level through HLH-30 activation and are required to protect metazoan upon PFT intoxication. Together, our data show a new and powerful connection between HLH-30-mediated autophagy and epithelium intrinsic cellular defense against the single most common mode of bacterial attack in vivo.
C. elegans, HLH-30/TFEB, autophagy, effector triggered immunity (ETI), intrinsic cellular defense (INCED), pore-forming toxin (PFT), surveillance immunity
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Copyright © 2017 The Author(s). Published with license by Taylor and Francis.
DOI of Published Version
Autophagy. 2017 Feb;13(2):371-385. doi: 10.1080/15548627.2016.1256933. Epub 2016 Nov 22. Link to article on publisher's site
Chen H, Aroian RV, Chen C. (2017). HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans. Open Access Publications by UMass Chan Authors. https://doi.org/10.1080/15548627.2016.1256933. Retrieved from https://escholarship.umassmed.edu/oapubs/2972
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