Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and a conserved p38 MAPK cascade.
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.
Ziegler
Katja
K
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille cedex 9, France.
Kurz
C Léopold
CL
Cypowyj
Sophie
S
Couillault
Carole
C
Pophillat
Matthieu
M
Pujol
Nathalie
N
Ewbank
Jonathan J
JJ
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
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