title: Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut Epithelium to Pore-Forming Toxin Attack.
abstract: Besides digesting nutrients, the gut protects the host against invasion by pathogens. Enterocytes may be subjected to damage by both microbial and host defensive responses, causing their death. Here, we report a rapid epithelial response that alleviates infection stress and protects the enterocytes from the action of microbial virulence factors. Intestinal epithelia exposed to hemolysin, a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily conserved process of thinning followed by the recovery of their initial thickness within a few hours. In response to hemolysin attack, Drosophila melanogaster enterocytes extrude most of their apical cytoplasm, including damaged organelles such as mitochondria, yet do not lyse. We identify two secreted peptides, the expression of which requires CyclinJ, that mediate the recovery phase in which enterocytes regain their original shape and volume. Epithelial thinning and recovery constitute a fast and efficient response to intestinal infections, with pore-forming toxins acting as alarm signals.
authors.affiliation: Université de Strasbourg, CNRS, RIDI UPR 9022, 67000 Strasbourg, France. Electronic address: kwang-zin.lee@agrar.uni-giessen.de.
authors.forename: Kwang-Zin
authors.initials: KZ
authors.lastname: Lee
authors.affiliation: Université de Strasbourg, CNRS, RIDI UPR 9022, 67000 Strasbourg, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Lestradet
authors.affiliation: Université de Strasbourg, CNRS, RIDI UPR 9022, 67000 Strasbourg, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Socha
authors.affiliation: Université de Strasbourg, CNRS, RIDI UPR 9022, 67000 Strasbourg, France.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schirmeier
authors.affiliation: UMR 1347, Université de Bourgogne-Franche-Comté, 17 Rue Sully, BP 86 510, 21065 Dijon Cedex, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Schmitz
authors.affiliation: Inserm U1109, MN3T, 3 avenue Molière, 67200 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France; LabEx Medalis, Université de Strasbourg, 67000 Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Spenlé
authors.affiliation: Inserm U1109, MN3T, 3 avenue Molière, 67200 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France; LabEx Medalis, Université de Strasbourg, 67000 Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lefebvre
authors.affiliation: Institut de Génétique et de Biologie Moléculaire, CNRS/INSERM/University of Strasbourg-UMR 7104, 1 rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Keime
authors.affiliation: Université de Strasbourg, CNRS, RIDI UPR 9022, 67000 Strasbourg, France.
authors.forename: Wennida M
authors.initials: WM
authors.lastname: Yamba
authors.affiliation: Université de Strasbourg, CNRS, RIDI UPR 9022, 67000 Strasbourg, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Bou Aoun
authors.affiliation: Université de Strasbourg, CNRS, RIDI UPR 9022, 67000 Strasbourg, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Liegeois
authors.affiliation: Institut de Génétique et de Biologie Moléculaire, CNRS/INSERM/University of Strasbourg-UMR 7104, 1 rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Schwab
authors.affiliation: Inserm U1109, MN3T, 3 avenue Molière, 67200 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France; LabEx Medalis, Université de Strasbourg, 67000 Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Simon-Assmann
authors.affiliation: UMR 1347, Université de Bourgogne-Franche-Comté, 17 Rue Sully, BP 86 510, 21065 Dijon Cedex, France; Université de Bourgogne Franche-Comté, AgroSup Dijon, PAM UMR A 02.102, 21000 Dijon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dalle
authors.affiliation: Université de Strasbourg, CNRS, RIDI UPR 9022, 67000 Strasbourg, France. Electronic address: D.Ferrandon@ibmc-cnrs.unistra.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Ferrandon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004331:Drosophila melanogaster; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D006460:Hemolysin Proteins / Q000378:metabolism / Q000633:toxicity; D007410:Intestinal Diseases / Q000382:microbiology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008871:Microvilli / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D016868:Serratia Infections; D012706:Serratia marcescens / Q000378:metabolism / Q000472:pathogenicity; D013534:Survival; D057077:Varroidae; D037521:Virulence Factors
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D037521:Virulence Factors