A PAX6-regulated receptor tyrosine kinase pairs with a pseudokinase to activate immune defense upon oomycete recognition in <i>Caenorhabditis elegans</i>.

Abstract

Oomycetes were recently discovered as natural pathogens of <i>Caenorhabditis elegans,</i> and pathogen recognition alone was shown to be sufficient to activate a protective transcriptional program characterized by the expression of multiple <i>chitinase-like</i> (<i>chil</i>) genes. However, the molecular mechanisms underlying oomycete recognition in animals remain fully unknown. We performed here a forward genetic screen to uncover regulators of <i>chil</i> gene induction and found several independent loss-of-function alleles of <i>old-1</i> and <i>flor-1,</i> which encode receptor tyrosine kinases belonging to the <i>C. elegans</i>-specific KIN-16 family. We report that OLD-1 and FLOR-1 are both necessary for mounting the immune response and act in the epidermis. FLOR-1 is a pseudokinase that acts downstream of the active kinase OLD-1 and regulates OLD-1 levels at the plasma membrane. Interestingly, the <i>old-1</i> locus is adjacent to the <i>chil</i> genes in the <i>C. elegans</i> genome, thereby revealing a genetic cluster important for oomycete resistance. Furthermore, we demonstrate that <i>old-1</i> expression at the anterior side of the epidermis is regulated by the VAB-3/PAX6 transcription factor, well known for its role in visual system development in other animals. Taken together, our study reveals both conserved and species-specific factors shaping the activation and spatial characteristics of the immune response to oomycete recognition.