title: Tissue-specific activities of an immune signaling module regulate physiological responses to pathogenic and nutritional bacteria in C. elegans.
abstract: Microbes represent both an essential source of nutrition and a potential source of lethal infection to the nematode Caenorhabditis elegans. Immunity in C. elegans requires a signaling module comprised of orthologs of the mammalian Toll-interleukin-1 receptor (TIR) domain protein SARM, the mitogen-activated protein kinase kinase kinase (MAPKKK) ASK1, and MAPKK MKK3, which activates p38 MAPK. We determined that the SARM-ASK1-MKK3 module has dual tissue-specific roles in the C. elegans response to pathogens--in the cell-autonomous regulation of innate immunity and the neuroendocrine regulation of serotonin-dependent aversive behavior. SARM-ASK1-MKK3 signaling in the sensory nervous system also regulates egg-laying behavior that is dependent on bacteria provided as a nutrient source. Our data demonstrate that these physiological responses to bacteria share a common mechanism of signaling through the SARM-ASK1-MKK3 module and suggest the co-option of ancestral immune signaling pathways in the evolution of physiological responses to microbial pathogens and nutrients.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Shivers
authors.forename: Tristan
authors.initials: T
authors.lastname: Kooistra
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Chu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Pagano
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology*; D017173:Caenorhabditis elegans / Q000276:immunology* / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000276:immunology; D007113:Immunity, Innate; D048371:MAP Kinase Kinase 3 / Q000276:immunology; D048848:MAP Kinase Kinase Kinase 5 / Q000276:immunology; D009417:Nerve Tissue / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D043562:Receptors, G-Protein-Coupled; C485906:tir-1 protein, C elegans; D048848:MAP Kinase Kinase Kinase 5; D048371:MAP Kinase Kinase 3