Drury, Florence et al. (2021) International Worm Meeting "A novel pair of receptor tyrosine kinases are required for oomycete pathogen recognition by C. elegans and resistance to infection"

Martinez-Perez, Enrique, Montoya, Alex, Kramer, Holger, Grover, Manish, Pacheco, Sarai, Barkoulas, Michalis, Drury, Florence

[International Worm Meeting, 2021]

Over the past two decades, C. elegans has been used as a model to study innate immune responses to naturally infecting pathogens, such as viruses, bacteria, microsporidia and fungi. Studying natural C. elegans pathogens allows us to understand immune response pathways that have co-evolved alongside the pathogen, which may be pathogen-specific or more broadly conserved. We previously described a new natural oomycete infection of C. elegans by Myzocytiopsis humicola. Oomycetes are morphologically similar to fungi and cause disease in plants and animals, including humans. Phytophthora infestans is the most notorious oomycete, responsible for potato blight, which is thought to have resulted in the Irish Potato Famine. Animal oomycete infections are less well understood, leaving a niche that can be fulfilled by C. elegans as a tractable model host. We have found that C. elegans are able to detect an M. humicola extract and upregulate an immune response that appears to be unique to oomycete infection. Pathogen detection is likely to occur in sensory neurons, which in turn trigger a cross-tissue signalling cascade leading to upregulation of chitinase-like genes in the epidermis and structural changes in the cuticle that confer resistance to oomycete infection. Using a forward genetic approach, we have identified a pair of receptor tyrosine kinases expressed in the epidermis that are required for upregulation of chitinase-like genes. Loss of either of these RTKs leads to increased susceptibility to M. humicola infection, and overexpression of one results in constitutive activation of the downstream immune response pathway. Phosphoproteomic analysis upon extract treatment has identified RTK-dependent downstream phosphorylation events and highlighted genes that we are currently testing as to whether they play a role in mounting the immune response. By characterising the role and interactions of these RTKs, we can not only understand a novel pathogen recognition response pathway in C. elegans, but also potentially assess its relevance for other animal oomycete infections that are largely understudied.