title: TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM.
abstract: Both plants and animals respond to infection by synthesizing compounds that directly inhibit or kill invading pathogens. We report here the identification of infection-inducible antimicrobial peptides in Caenorhabditis elegans. Expression of two of these peptides, NLP-29 and NLP-31, was differentially regulated by fungal and bacterial infection and was controlled in part by tir-1, which encodes an ortholog of SARM, a Toll-interleukin 1 receptor (TIR) domain protein. Inactivation of tir-1 by RNA interference caused increased susceptibility to infection. We identify protein partners for TIR-1 and show that the small GTPase Rab1 and the f subunit of ATP synthase participate specifically in the control of antimicrobial peptide gene expression. As the activity of tir-1 was independent of the single nematode Toll-like receptor, TIR-1 may represent a component of a previously uncharacterized, but conserved, innate immune signaling pathway.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale/Centre National de la Recherche Scientifique/Université de la Méditerranée, Case 906, 13288 Marseille Cedex 9, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Couillault
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pujol
authors.forename: Jérôme
authors.initials: J
authors.lastname: Reboul
authors.forename: Laurence
authors.initials: L
authors.lastname: Sabatier
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Guichou
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kohara
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Ewbank
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D051186:Armadillo Domain Proteins; D017173:Caenorhabditis elegans / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009181:Mycoses / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D051193:Toll-Like Receptors
chemical_list: D023181:Antimicrobial Cationic Peptides; D051186:Armadillo Domain Proteins; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C435689:SARM1 protein, human; D051193:Toll-Like Receptors; C485906:tir-1 protein, C elegans