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Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2004 Apr 27; Vol. 101 (17), pp. 6593-8. - Publication Year :
- 2004
-
Abstract
- The p38 mitogen-activated protein kinase pathway regulates innate immune responses in evolutionarily diverse species. We have previously shown that the Caenorhabditis elegans p38 mitogen-activated protein kinase, PMK-1, functions in an innate immune response pathway that mediates resistance to a variety of microbial pathogens. Here, we show that tir-1, a gene encoding a highly conserved Toll/IL-1 resistance (TIR) domain protein, is also required for C. elegans resistance to microbial pathogens. RNA interference inactivation of tir-1 resulted in enhanced susceptibility to killing by pathogens and correspondingly diminished PMK-1 phosphorylation. Unlike all known TIR-domain adapter proteins, overexpression of the human TIR-1 homologue, SARM, in mammalian cells was not sufficient to induce expression of NF-kappaB or IRF3-dependent reporter genes that are activated by Toll-like receptor signaling. These data reveal the involvement of a previously uncharacterized, evolutionarily conserved TIR domain protein in innate immunity that is functionally distinct from other known TIR domain signaling adapters.
- Subjects :
- Animals
Base Sequence
Caenorhabditis elegans genetics
DNA Primers
Enzyme Activation
Gene Expression Regulation
Membrane Glycoproteins genetics
Mitogen-Activated Protein Kinases metabolism
Receptors, Interleukin-1 genetics
Signal Transduction
p38 Mitogen-Activated Protein Kinases
Caenorhabditis elegans immunology
Membrane Glycoproteins physiology
Receptors, Interleukin-1 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 101
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 15123841
- Full Text :
- https://doi.org/10.1073/pnas.0308625101