title: Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and a conserved p38 MAPK cascade.
abstract: 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.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille cedex 9, France.
authors.forename: Katja
authors.initials: K
authors.lastname: Ziegler
authors.forename: C Léopold
authors.initials: CL
authors.lastname: Kurz
authors.forename: Sophie
authors.initials: S
authors.lastname: Cypowyj
authors.forename: Carole
authors.initials: C
authors.lastname: Couillault
authors.forename: Matthieu
authors.initials: M
authors.lastname: Pophillat
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pujol
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Ewbank
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000276:immunology*; D029742:Caenorhabditis elegans Proteins / Q000276:immunology* / Q000378:metabolism*; D005658:Fungi / Q000276:immunology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D007113:Immunity, Innate; D008954:Models, Biological; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: D029742:Caenorhabditis elegans Proteins; C095371:TPA-1 protein, C elegans; D011505:Protein-Tyrosine Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins