Reference - Detail
|Author||Ziegler K, Kurz CL, Cypowyj S, Couillault C, Pophillat M, Pujol N, Ewbank JJ.|
|Title||Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and a conserved p38 MAPK cascade.|
|Journal||Cell Host Microbe|
Like other multicellular organisms, the model nematode C. elegans responds to infection by inducing the expression of defense genes. Among the genes upregulated in response to a natural fungal pathogen is nlp-29, encoding an antimicrobial peptide. In a screen for mutants that fail to express nlp-29 following fungal infection, we isolated alleles of tpa-1, homologous to the mammalian protein kinase C (PKC) delta. Through epistasis analyses, we demonstrate that C. elegans PKC acts through the p38 MAPK pathway to regulate nlp-29. This involves G protein signaling and specific C-type phospholipases acting upstream of PKCdelta. Unexpectedly and unlike in mammals, tpa-1 does not act via D-type protein kinases, but another C. elegans PKC gene, pkc-3, functions nonredundantly with tpa-1 to control nlp-29 expression. Finally, the tribbles-like kinase nipi-3 acts upstream of PKCdelta in this antifungal immune signaling cascade. These findings greatly expand our understanding of the pathways involved in C. elegans innate immunity.
|MeSH||Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / immunology* Caenorhabditis elegans Proteins / immunology* Caenorhabditis elegans Proteins / metabolism* Fungi / immunology* GTP-Binding Proteins / metabolism Gene Expression Regulation, Fungal Immunity, Innate* Models, Biological Protein Kinase C / metabolism Protein-Tyrosine Kinases / immunology* Protein-Tyrosine Kinases / metabolism* Signal Transduction Type C Phospholipases / metabolism p38 Mitogen-Activated Protein Kinases / immunology|
|WOS Category||PARASITOLOGY MICROBIOLOGY VIROLOGY|