The spores of the nematophagous fungus Drechmeria coniospora adhere to the cuticle of C. elegans. They produce penetration tubes that transverse its cuticle and develop into trophic hyphae that colonize the epidermis. C. elegans responds to this infection by up-regulating many genes in the epidermis, including certain members of the nlp gene family that encode putative antimicrobial peptides (AMPs). This induction can be visualized using reporter genes, such as
pnlp-29::GFP. In addition to infection, sterile injury and high salt also markedly increase expression of
pnlp-29::GFP. We performed a direct genetic screen for mutants that do not show up-regulation of the AMP gene
nlp-29 upon infection. Among the alleles isolated, two (
fr1 and
fr3) failed to complement each other. Both block the response to infection and injury, but show a normal response to osmotic stress. We identified the mutations as new alleles of
tpa-1. This well-studied gene encodes a protein kinase C (PKC), homologous to mammalian PKC delta. PKC can be activated by diacylglycerol (DAG), or by the DAG mimetic phorbol 12-myristate 13-acetate (PMA). As expected, PMA alone strongly induced the expression of
nlp-29 in wild-type worms, but not in
tpa-1 mutants. The PMA-induced expression of
nlp-29 was similarly blocked in
tir-1,
nsy-1,
sek-1 and
pmk-1 mutants. These genes all encode components of a
p38 MAPK cascade that we have shown to regulate
nlp-29 expression after infection. These results and further epistasis analyses place the
p38 MAPK pathway downstream of the PKC TPA-1. We also found that the induction of
nlp-29 after infection was blocked by mutations in the genes
egl-8 and
plc-3, which encode phospholipases C that act up-stream of
tpa-1. This suggests that activation of a G-protein coupled receptor may initiate the response to fungal infection.