title: Screening in planarians identifies MORN2 as a key component in LC3-associated phagocytosis and resistance to bacterial infection.
abstract: Dugesia japonica planarian flatworms are naturally exposed to various microbes but typically survive this challenge. We show that planarians eliminate bacteria pathogenic to Homo sapiens, Caenorhabditis elegans, and/or Drosophila melanogaster and thus represent a model to identify innate resistance mechanisms. Whole-transcriptome analysis coupled with RNAi screening of worms infected with Staphylococcus aureus or Legionella pneumophila identified 18 resistance genes with nine human orthologs, of which we examined the function of MORN2. Human MORN2 facilitates phagocytosis-mediated restriction of Mycobacterium tuberculosis, L. pneumophila, and S. aureus in macrophages. MORN2 promotes the recruitment of LC3, an autophagy protein also involved in phagocytosis, to M. tuberculosis-containing phagosomes and subsequent maturation to degradative phagolysosomes. MORN2-driven trafficking of M. tuberculosis to single-membrane, LC3-positive compartments requires autophagy-related proteins Atg5 and Beclin-1, but not Ulk-1 and Atg13, highlighting the importance of MORN2 in LC3-associated phagocytosis. These findings underscore the value of studying planarian defenses to identify immune factors.
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France; INSERM, U1065, C3M, Université de Nice Sophia-Antipolis, Equipe labellisée ligue contre le cancer, 06204 Nice Cedex 3, France.
authors.forename: Prasad
authors.initials: P
authors.lastname: Abnave
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France; Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II," Via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mottola
authors.affiliation: Otago Genomics & Bioinformatics Facility, Department of Biochemistry, University of Otago, PO Box 56, 710 Cumberland Street, Dunedin 9054, New Zealand.
authors.forename: Gregory
authors.initials: G
authors.lastname: Gimenez
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boucherit
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Trouplin
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Torre
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France; INSERM, U1065, C3M, Université de Nice Sophia-Antipolis, Equipe labellisée ligue contre le cancer, 06204 Nice Cedex 3, France.
authors.forename: Filippo
authors.initials: F
authors.lastname: Conti
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France.
authors.forename: Amira
authors.initials: A
authors.lastname: Ben Amara
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lepolard
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Djian
authors.affiliation: INSERM, U1065, C3M, Université de Nice Sophia-Antipolis, Equipe labellisée ligue contre le cancer, 06204 Nice Cedex 3, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hamaoui
authors.affiliation: INSERM, U1065, C3M, Université de Nice Sophia-Antipolis, Equipe labellisée ligue contre le cancer, 06204 Nice Cedex 3, France.
authors.forename: Amel
authors.initials: A
authors.lastname: Mettouchi
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France; INSERM, U1065, C3M, Université de Nice Sophia-Antipolis, Equipe labellisée ligue contre le cancer, 06204 Nice Cedex 3, France.
authors.forename: Atul
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Centre Commun de Microscopie Appliquée (CCMA) Université de Nice Sophia Antipolis, Faculté des Sciences, Parc Valrose, 06108 Nice Cedex 2, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Pagnotta
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II," Via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonatti
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Lepidi
authors.affiliation: Department of Clinical and Experimental Medicine, Unity of Experimental Biology and Genetics, University of Pisa, Via Volta 4, 56126 Pisa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Salvetti
authors.affiliation: Centre National de la Recherche Scientifique, Laboratoire d'Analyse, Topologie, Probabilités - Unité Mixte de Recherche 7353, Equipe ATIP, Aix-Marseille Université, 13331 Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Abi-Rached
authors.affiliation: INSERM, U1065, C3M, Université de Nice Sophia-Antipolis, Equipe labellisée ligue contre le cancer, 06204 Nice Cedex 3, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lemichez
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mege
authors.affiliation: CNRS UMR 7278, IRD198, INSERM U1095, Aix-Marseille Université, 27 Bd Jean Moulin 13385 Marseille Cedex 05, France. Electronic address: eric.ghigo@univ-amu.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Ghigo
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016952:Legionella pneumophila / Q000276:immunology / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology*; D010587:Phagocytosis; D010932:Planarians / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000276:immunology / Q000502:physiology*
chemical_list: D015801:Helminth Proteins; D008869:Microtubule-Associated Proteins