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

被引：84

作者：

Abnave, Prasad ^{[1
,7
]}

Mottola, Giovanna ^{[1
,2
]}

Gimenez, Gregory ^{[3
]}

Boucherit, Nicolas ^{[1
]}

Trouplin, Virginie ^{[1
]}

Torre, Cedric ^{[1
]}

Conti, Filippo ^{[1
,7
]}

Ben Amara, Amira ^{[1
]}

Lepolard, Catherine ^{[1
]}

Djian, Benjamin ^{[1
]}

Hamaoui, Daniel

Mettouchi, Amel

Kumar, Atul ^{[1
]}

Pagnotta, Sophie ^{[4
]}

Bonatti, Stefano ^{[2
]}

Lepidi, Hubert ^{[1
]}

Salvetti, Alessandra ^{[5
]}

Abi-Rached, Laurent ^{[6
]}

Lemichez, Emmanuel ^{[7
]}

Mege, Jean-Louis ^{[1
]}

Ghigo, Eric ^{[1
]}

机构：

[1] Aix Marseille Univ, INSERM U1095, IRD198, CNRS UMR 7278, F-13385 Marseille 05, France

[2] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, I-80131 Naples, Italy

[3] Univ Otago, Dept Biochem, Otago Genom & Bioinformat Facil, Dunedin 9054, New Zealand

[4] Univ Nice Sophia Antipolis, Fac Sci, CCMA, F-06108 Nice 2, France

[5] Univ Pisa, Dept Clin & Expt Med, I-56126 Pisa, Italy

[6] Aix Marseille Univ, CNRS, Lab Anal Topol Probabil, Unite Mixte Rech 7353,Equipe ATIP, F-13331 Marseille 05, France

[7] Univ Nice Sophia Antipolis, C3M, INSERM U1065, F-06204 Nice 3, France

来源：

CELL HOST & MICROBE | 2014年 / 16卷 / 03期

关键词：

CAENORHABDITIS-ELEGANS; MODEL HOST; BACILLUS-THURINGIENSIS; MYCOBACTERIUM-TUBERCULOSIS; DROSOPHILA-MELANOGASTER; NONCANONICAL AUTOPHAGY; VIRULENCE; PATHOGENICITY; SUBVERSION; MACHINERY;

D O I：

10.1016/j.chom.2014.08.002

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：338 / 350

页数：13

共 62 条

[1] Double-stranded RNA specifically disrupts gene expression during planarian regeneration [J].