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

Abstract

Simple SummaryAll organisms, from bacteria to mammals, activate responses protecting themselves from dangers represented by outsider invaders and damages. Inappropriately localised self-DNA is one of the molecular clues detected as a danger and triggering defence reactions that may lead to chronic activation of inflammatory conditions. In this study, we investigate if dietary delivered self-DNA is detrimental in a simple metazoan model organism, the nematode Caenorhabditis elegans. Adverse effects were observed in the progenies of worms exposed to self-DNA integrated into their bacterial diet. The presence of self-DNA in the food significantly decreased egg deposition, induced high embryo death, and negatively affected larval development. The findings, on the one side, raise interesting questions on the basic molecular mechanisms involved in response to extracellular self-DNA. On the other side, the observed phenomenon suggests possible applications for the biocontrol of parasitic nematodes by appropriate delivery of their self-DNA in their growing environment.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 DNA-sensing 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 affects embryogenesis, 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 model organism were not pursued up to now. The genetic tractability of C. elegans will help to identify the basic molecular pathways involved in such mechanisms. The specificity of the adverse effects associated with a self-DNA enriched diet suggests applications in biological pest control approaches.