title: HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans.
abstract: 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.
authors.affiliation: a Department of Biochemistry and Molecular Biology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.|b Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University , Tainan , Taiwan.
authors.forename: Huan-Da
authors.initials: HD
authors.lastname: Chen
authors.affiliation: c Immunology Research Center, National Health Research Institutes , Miaoli , Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Kao
authors.affiliation: a Department of Biochemistry and Molecular Biology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.
authors.forename: Bang-Yu
authors.initials: BY
authors.lastname: Liu
authors.affiliation: a Department of Biochemistry and Molecular Biology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.
authors.forename: Shin-Whei
authors.initials: SW
authors.lastname: Huang
authors.affiliation: a Department of Biochemistry and Molecular Biology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.|b Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University , Tainan , Taiwan.
authors.forename: Cheng-Ju
authors.initials: CJ
authors.lastname: Kuo
authors.affiliation: c Immunology Research Center, National Health Research Institutes , Miaoli , Taiwan.
authors.forename: Jhen-Wei
authors.initials: JW
authors.lastname: Ruan
authors.affiliation: d Institute of Biotechnology, National Tsing Hua University , Hsinchu , Taiwan.
authors.forename: Yen-Hung
authors.initials: YH
authors.lastname: Lin
authors.affiliation: a Department of Biochemistry and Molecular Biology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.
authors.forename: Cheng-Rung
authors.initials: CR
authors.lastname: Huang
authors.affiliation: a Department of Biochemistry and Molecular Biology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.|e School of Medicine, College of Medicine, National Cheng Kung University , Tainan , Taiwan.
authors.forename: Yu-Hung
authors.initials: YH
authors.lastname: Chen
authors.affiliation: d Institute of Biotechnology, National Tsing Hua University , Hsinchu , Taiwan.
authors.forename: Horng-Dar
authors.initials: HD
authors.lastname: Wang
authors.affiliation: f Program in Molecular Medicine, University of Massachusetts Medical School , Worcester , MA , USA.
authors.forename: Raffi V
authors.initials: RV
authors.lastname: Aroian
authors.affiliation: a Department of Biochemistry and Molecular Biology , College of Medicine, National Cheng Kung University , Tainan , Taiwan.|b Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University , Tainan , Taiwan.
authors.forename: Chang-Shi
authors.initials: CS
authors.lastname: Chen
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D000071183:Autophagy-Related Proteins / Q000235:genetics / Q000378:metabolism; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins / Q000633:toxicity*; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004731:Endotoxins / Q000633:toxicity*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D006460:Hemolysin Proteins / Q000633:toxicity*; D007422:Intestines / Q000382:microbiology / Q000473:pathology; D008954:Models, Biological; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000071183:Autophagy-Related Proteins; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins; D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D004731:Endotoxins; D006460:Hemolysin Proteins; C583069:HLH-30 protein, C elegans; C030956:insecticidal crystal protein, Bacillus Thuringiensis
keywords: C. elegans; HLH-30/TFEB; autophagy; effector triggered immunity (ETI); intrinsic cellular defense (INCED); pore-forming toxin (PFT); surveillance immunity