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.

Transcriptional profiling of the peripheral blood response during tularemia

“…10 Although its role in anti-bacterial defense is unknown, it is co-regulated with TIR-1, which is important to the defense of Caenorhabditis elegans against bacterial infections. 11 An activator of caspase-mediated apoptosis, TNFSF10 (TRAIL), is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. It was strongly upregulated at the first time point.…”

MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

“…TIR-1 was hypothesized to mediate signaling from TOL-1, which is the only TLR homologue. Indeed, knockdown of tir-1 shortened the lifespan of worms feeding on Drechmeria coniospora , Serratia marcescens ( 16 ), Pseudomonas aeruginosa, and Enterococcus faecalis ( 17 ). However, this eff ect was independent of TOL-1 ( 16 ).…”

“…Indeed, knockdown of tir-1 shortened the lifespan of worms feeding on Drechmeria coniospora , Serratia marcescens ( 16 ), Pseudomonas aeruginosa, and Enterococcus faecalis ( 17 ). However, this eff ect was independent of TOL-1 ( 16 ). Thus, rather than mediating signaling from TOL-1, TIR-1 may have controlled recognition of environmental cues derived from the pathogenic bacteria.…”

Genome-wide identification of lineage-specific genes within Caenorhabditis elegans

“…Subsequent functional analysis in silico showed that 9.5% of SSGs and 31.5% of GSGs have been annotated and classified. Among the annotated LSGs, the proteins (F-box protein, C-type lectin, Caenacin, insulin-like peptide, C. elegans homeobox, and neuropeptide-like protein) related to sex determination [32], specific stress [36], immune response [34,35,38,40], growth factor [39], morphogenesis [31,33], and behavior [37] are considerably over-represented in LSGs. For previously unannotated LSGs, we used ProtFun2.2 to predict their functions (cellular roles and GO categories).…”

“…We classified them into different groups based on gene class description and calculated the gene number in each group. The results indicated that the functions, related to sex determination, specific stress, immune response, growth factor, morphogenesis, and behavior [31][32][33][34][35][36][37][38][39][40] The vertical axis represents the proportion of genes with each exon-intron structure compared with total SSGs, GSGs, or ECs (evolutionarily conserved genes), whereas, the abscissa axis represents the types of exon-intron structure.…”