Reference - Detail
|Author||Pujol N, Cypowyj S, Ziegler K, Millet A, Astrain A, Goncharov A, Jin Y, Chisholm AD, Ewbank JJ.|
|Title||Distinct innate immune responses to infection and wounding in the C. elegans epidermis.|
BACKGROUND:In many animals, the epidermis is in permanent contact with the environment and represents a first line of defense against pathogens and injury. Infection of the nematode Caenorhabditis elegans by the natural fungal pathogen Drechmeria coniospora induces the expression in the epidermis of antimicrobial peptide (AMP) genes such as nlp-29. Here, we tested the hypothesis that injury might also alter AMP gene expression and sought to characterize the mechanisms that regulate the innate immune response.
RESULTS:Injury induces a wound-healing response in C. elegans that includes induction of nlp-29 in the epidermis. We find that a conserved p38-MAP kinase cascade is required in the epidermis for the response to both infection and wounding. Through a forward genetic screen, we isolated mutants that failed to induce nlp-29 expression after D. coniospora infection. We identify a kinase, NIPI-3, related to human Tribbles homolog 1, that is likely to act upstream of the MAPKK SEK-1. We find NIPI-3 is required only for nlp-29 induction after infection and not after wounding.
CONCLUSIONS:Our results show that the C. elegans epidermis actively responds to wounding and infection via distinct pathways that converge on a conserved signaling cassette that controls the expression of the AMP gene nlp-29. A comparison between these results and MAP kinase signaling in yeast gives insights into the possible origin and evolution of innate immunity.
|MeSH||Amino Acid Sequence Animals Antimicrobial Cationic Peptides / genetics Antimicrobial Cationic Peptides / metabolism Caenorhabditis elegans / genetics Caenorhabditis elegans / immunology* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / metabolism Epidermis / immunology* Immunity, Innate / physiology* Infection / immunology* Infection / metabolism Molecular Sequence Data Neuropeptides / metabolism Protein Kinases / metabolism Signal Transduction / physiology Up-Regulation Wound Healing / physiology* p38 Mitogen-Activated Protein Kinases / metabolism|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY|