A receptor tyrosine kinase regulated by the transcription factor VAB-3/PAX6 pairs with a pseudokinase to trigger immune signalling upon oomycete recognition in C. elegans

Oomycetes were recently discovered as natural pathogens of Caenorhabditis elegans and pathogen recognition alone was shown to be sufficient to activate a protective transcriptional program in the host characterised by the expression of multiple chitinase-like (chil) genes. However, the molecular mechanisms underlying oomycete recognition in animals remain fully unknown. We performed here a forward genetic screen to uncover regulators of chil gene induction and found several independent loss-of-function alleles of old-1 and flor-1, which encode receptor tyrosine kinases belonging to the C. elegans-specific KIN-16 family. We present evidence that OLD-1 is an active kinase mounting the immune response, and FLOR-1 a pseudokinase that is also required for the response and regulates the distribution of OLD-1 at the epidermal membrane. Interestingly, the old-1 locus is adjacent to the chil genes in the nematode genome, thereby revealing a genetic cluster important for oomycete-resistance. Furthermore, we identify the VAB-3/PAX-6 transcription factor known for its role in visual system development to regulate old-1 expression, and consequently the spatial pattern of the response to oomycete recognition. Taken together, our study reveals both conserved and species-specific factors shaping the response to oomycete recognition.