Paired C-type lectin receptors mediate specific recognition of divergent oomycete pathogens in C. elegans

Innate immune responses can be initiated through the detection of pathogen or damage-associated molecular patterns by host receptors that are often present on the surface of immune cells. While certain invertebrates like Caenorhabditis elegans lack professional immune cells, they still respond to infection in a pathogen-specific manner. It has been debated for years whether homologues of the canonical pathogen recognition receptors are also functioning in the nematode. Here we show that C-type lectin receptors mediate species-specific recognition of divergent oomycetes in C. elegans. A CLEC-27/CLEC-35 pair is essential for recognition of the oomycete Myzocytiopsis humicola , while a CLEC-26/CLEC-36 pair is required for detection of Haptoglossa zoospora. Both clec pairs are transcriptionally regulated through a shared promoter by the conserved PRD-like homeodomain transcription factor CEH-37/OTX2 and act in sensory neurons and the anterior intestine to trigger a protective immune response in the epidermis. This system enables redundant tissue sensing of oomycete threats through canonical CLEC receptors and host defense via cross-tissue communication.