Screening in Planarians Identifies MORN2 as a Key Component in LC3-Associated Phagocytosis and Resistance to Bacterial Infection

• Published in: Cell host & microbe 2014-09, Vol.16 (3), p.338-350
• Main Authors: Abnave, Prasad, Mottola, Giovanna, Gimenez, Gregory, Boucherit, Nicolas, Trouplin, Virginie, Torre, Cedric, Conti, Filippo, Ben Amara, Amira, Lepolard, Catherine, Djian, Benjamin, Hamaoui, Daniel, Mettouchi, Amel, Kumar, Atul, Pagnotta, Sophie, Bonatti, Stefano, Lepidi, Hubert, Salvetti, Alessandra, Abi-Rached, Laurent, Lemichez, Emmanuel, Mege, Jean-Louis, Ghigo, Eric
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Infections - genetics; Bacterial Infections - immunology; Bacterial Infections - microbiology; Disease Models, Animal; Helminth Proteins - genetics; Helminth Proteins - immunology; Humans; Legionella pneumophila - immunology; Legionella pneumophila - physiology; Life Sciences; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - immunology; Phagocytosis; Planarians - genetics; Planarians - immunology; Planarians - microbiology; Staphylococcus aureus - immunology; Staphylococcus aureus - physiology
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2014.08.002

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. [Display omitted] •Dugesia japonica planarian flatworms eliminate a spectrum of ingested pathogenic bacteria•Transcriptomic and RNAi analyses reveal planarian genes promoting resistance to bacteria•MORN2 restricts the growth of all bacterial strains tested in planarians•MORN2 promotes lipidation of LC3-I and LC3-associated phagocytosis of M. tuberculosis Dugesia japonica planarian flatworms are resistant to various bacteria that are pathogenic in humans. Abnave et al. use planarians as a model to identify antibacterial immune factors and determine that MORN2, conserved in Homo sapiens, restricts intracellular bacterial growth by promoting LC3-associated phagocytosis of invading bacteria.