Self-DNA Exposure Induces Developmental Defects and Germline DNA Damage Response in Caenorhabditis elegans

All organisms, from bacteria to mammals, sense and respond to foreign nucleic acids to fight infections in order to survive and preserve genome integrity across generations. The innate immune system is an evolutionarily conserved defence strategy. Complex organisms have developed various cellular processes to respond to and recognise not only infections, i.e., pathogen-associated molecular patterns (PAMPs), but also to sense injury and tissue dysfunctions, i.e., damage-associated molecular patterns (DAMPs). Mis-localized self-DNA can be sensed as DAMP by specific DNAsensing pathways, and self-DNA chronic exposure can be detrimental to the organisms. Here,we investigate the effects of dietary delivered self-DNA in the nematode Caenorhabditis elegans.The hermaphrodite worms were fed on Escherichia coli genomic libraries: a C. elegans library (self)and a legume (Medicago truncatula) library (non-self). We show that the self-library diet affectsembryogenesis, larval development and gametogenesis. DNA damage and activation of p53/CEP-1-dependent apoptosis occur in gonadal germ cells. Studies of self-DNA exposure in this modelorganism were not pursued up to now. The genetic tractability of C. elegans will help to identifythe basic molecular pathways involved in such mechanisms. The specificity of the adverse effectsassociated with a self-DNA enriched diet suggests applications in biological pest control approaches.