title: Genetic Screen Reveals Link between the Maternal Effect Sterile Gene mes-1 and Pseudomonas aeruginosa-induced Neurodegeneration in Caenorhabditis elegans.
abstract: Increasing evidence indicates that immune responses to microbial infections may contribute to neurodegenerative diseases. Here, we show that Pseudomonas aeruginosa infection of Caenorhabditis elegans causes a number of neural changes that are hallmarks of neurodegeneration. Using an unbiased genetic screen to identify genes involved in the control of P. aeruginosa-induced neurodegeneration, we identified mes-1, which encodes a receptor tyrosine kinase-like protein that is required for unequal cell divisions in the early embryonic germ line. We showed that sterile but not fertile mes-1 animals were resistant to neurodegeneration induced by P. aeruginosa infection. Similar results were observed using animals carrying a mutation in the maternal effect gene pgl-1, which is required for postembryonic germ line development, and the germ line-deficient strains glp-1 and glp-4. Additional studies indicated that the FOXO transcription factor DAF-16 is required for resistance to P. aeruginosa-induced neurodegeneration in germ line-deficient strains. Thus, our results demonstrate that P. aeruginosa infection results in neurodegeneration phenotypes in C. elegans that are controlled by the germ line in a cell-nonautonomous manner.
authors.affiliation: From the Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710 and the Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Qiuli
authors.initials: Q
authors.lastname: Wu
authors.affiliation: From the Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710 and.
authors.forename: Xiou
authors.initials: X
authors.lastname: Cao
authors.affiliation: From the Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710 and.
authors.forename: Dong
authors.initials: D
authors.lastname: Yan
authors.affiliation: the Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Wang
authors.affiliation: From the Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710 and a.aballay@duke.edu.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Aballay
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002633:Chemotaxis; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000382:microbiology*; D009997:Osmotic Pressure; D010641:Phenotype; D011552:Pseudomonas Infections / Q000235:genetics*; D011550:Pseudomonas aeruginosa; D034622:RNA Interference
chemical_list: D029742:Caenorhabditis elegans Proteins; C415743:Mes-1 protein, C elegans; D049452:Green Fluorescent Proteins
keywords: Caenorhabditis elegans (C. elegans); P. aeruginosa infection; germ line; host-pathogen interaction; infection; innate immunity; mes-1; neurodegeneration; pathogen-induced neurodegeneration