The C. elegans
tir-1 gene encodes a conserved Toll-Interleukin-1 Receptor (TIR) domain adaptor protein that has N-terminal HEAT/Armadillo repeats, two Sterile-alpha motifs (SAM domains), and a C-terminal TIR domain. The
tir-1 locus is expressed as at least 6 isoforms that include 3 long isoforms (
tir-1a,
tir-1c and
tir-1e) and three short isoforms (
tir-1b,
tir-1d and
tir-1f) [1]. RNAi knockdown experiments targeting a region of the gene common to all isoforms of
tir-1 causes an enhanced susceptibility to pathogen (Esp) phenotype [2, 3]. We have observed that previously described
tir-1 mutant alleles,
tm1111 and
ok1052, which specifically disrupt the long isoforms do not affect pathogen susceptibility, although these mutants exhibit aberrant signaling in a cell fate decision in AWC neuronal development [1]. We report the isolation and characterization of two
tir-1 mutant alleles (
qd2 and
qd4) that disrupt the TIR domain and confer an Esp phenotype. These
tir-1 alleles have allowed us to define the functional domains of TIR-1 required for pathogen resistance, revealing that the SAM and TIR domains of the protein are sufficient for the function of TIR-1 in immunity. In addition, we have carried out tissue-specific rescue experiments that suggest that TIR-1 functions in the intestine in conjunction with PMK-1 pathway components to confer resistance to intestinal infection. Epistasis analysis of
tir-1 mutant alleles and mutants affecting components of the NSY-1-SEK-1-PMK-1
p38 MAPK pathway [4] suggests that TIR-1 functions redundantly with additional parallel inputs upstream of the PMK-1 pathway in pathogen resistance. 1.Chuang, C.F. and C.I. Bargmann. Genes Dev, 2005. 19(2): p. 270-81. 2.Couillault, C., et al. Nat Immunol, 2004. 5(5): p. 488-94. 3.Liberati, N.T., et al. Proc Natl Acad Sci U S A, 2004. 101(17): p. 6593-8. 4.Kim, D.H., et al. Science, 2002. 297(5581): p. 623-6.