title: Conserved nutrient sensor O-GlcNAc transferase is integral to C. elegans pathogen-specific immunity.
abstract: Discriminating pathogenic bacteria from bacteria used as a food source is key to Caenorhabidits elegans immunity. Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the C. elegans innate immune response. Genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. Genetic interaction studies revealed that nutrient-responsive OGT-1 acts through the conserved β-catenin (BAR-1) pathway and in concert with p38 MAPK (PMK-1) to modulate the immune response to S. aureus. Moreover, whole genome transcriptional profiling revealed that O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes. The participation of nutrient sensor OGT-1 in an immunity module evolutionarily conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Bond
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Salil K
authors.initials: SK
authors.lastname: Ghosh
authors.affiliation: Department of Pathology, Medstar Georgetown University Hospital, Washington, District of Columbia, United States of America.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: Hanover
mesh_terms: D000117:Acetylglucosamine; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D005502:Food; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013211:Staphylococcus aureus / Q000276:immunology / Q000472:pathogenicity; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D051176:beta Catenin; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D048051:p38 Mitogen-Activated Protein Kinases; D000117:Acetylglucosamine