The soil nematode Caenorhabditis elegans in the wild encounters various pathogens and pathobionts. However they lack the evolutionarily conserved toll-like receptors (TLRs) for pathogen recognition and defense suggesting that the worm may employ alternative strategies for pathogen resistance. However very little is known about the molecular mechanisms that regulate worm immunity. Using an image based RNAi screen for increased gut colonization with the pathogenic bacteria Pseudomonas aeruginosa, we identified PDFR-1; a G-protein coupled receptor and its endogenous ligands PDF-1 and PDF-2 to be essential for pathogen defense. Interestingly, we show that the ligands are only upregulated in intestine following the infection and activate the receptor in sensory neurons, signifying that there is a gut-brain cross talk during infection. This may either trigger the worm’s flight response or lead to expression of downstream immune effectors contributing to the host defense.
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