TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM

Nat Immunol. 2004 May;5(5):488-94. doi: 10.1038/ni1060. Epub 2004 Mar 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / metabolism
  • Armadillo Domain Proteins
  • Caenorhabditis elegans / immunology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / microbiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology*
  • Membrane Glycoproteins / metabolism
  • Molecular Sequence Data
  • Mycoses / immunology
  • Mycoses / metabolism
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled
  • Toll-Like Receptors


  • Antimicrobial Cationic Peptides
  • Armadillo Domain Proteins
  • Caenorhabditis elegans Proteins
  • Cytoskeletal Proteins
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • SARM1 protein, human
  • Toll-Like Receptors
  • tir-1 protein, C elegans