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

Abstract

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.

Effects of Extracellular Self- and Nonself-DNA on the Freshwater Microalga Chlamydomonas reinhardtii and on the Marine Microalga Nannochloropsis gaditana

“…Similarly, in tomato, the ubiquinol oxidase and catalase, which are major ROS scavengers in plants, were found downregulated in response to the treatment with self-exDNA [ 88 ], and this is probably directly correlated to the increased ROS production together with an impaired removal observed in tomato leaves. Interestingly, a very recent investigation highlighted that the treatment with self-exDNA in the model organism Caenorhabditis elegans affects reproductive behavior inducing cell damage and cell death [ 107 ], revealed by double-strand breaks demonstrated by the activation of RAD-51 and apoptotic nuclei.…”

The CpG-dependent plant immune response to self-DNA triggers defence hormone signalling and improves fitness

“…For example, studies using A. thaliana, common bean (Phaseolus vulgaris), lima bean (Phaseolus lunatus), lettuce (Lactuca sativa), maize (Zea mays) and tomato (Solanum lycopersicum) reported that treatment with fragmented self-DNA triggered Ca 2+ fluxes, membrane depolarization, the activation of mitogen-activated protein kinases (MAPKs), the formation of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), the expression of diverse resistance-related genes, the secretion of extrafloral nectar [an indirect defence against chewing herbivores that is controlled by the 'wound hormone', jasmonic acid (JA)], and also phenotypic resistance to biological enemies including pathogenic bacteria (Pseudomonas syringae) and fungi (Botrytis cinerea), the aphid Myzus persicae and the oomycete Hyaloperonospora arabidopsidis [15][16][17][18][19] .Intriguingly, these latter studies reported stronger immune responses to self-as compared to non-self-DNA. Moreover, accumulating evidence characterises the 'Mazzoleni-effect' (a dosage-dependent inhibition of growth by self-DNA, but not non-self -DNA) as a seemingly universal feature of organisms across the tree of life 7,15,17,[20][21][22][23] . Immune responses to self-derived molecules seemingly contradict the general immunological paradigm that expects immune responses to non-self because "The immune system evolved to discriminate infectious nonself from noninfectious self" 24 , but they support the danger model of Polly Matzinger, who argues that "the immune system is more concerned with entities that do damage than with those that are foreign" 25 .…”

“…Intriguingly, these latter studies reported stronger immune responses to self-as compared to non-self-DNA. Moreover, accumulating evidence characterises the 'Mazzoleni-effect' (a dosage-dependent inhibition of growth by self-DNA, but not non-self -DNA) as a seemingly universal feature of organisms across the tree of life 7,15,17,[20][21][22][23] . Immune responses to self-derived molecules seemingly contradict the general immunological paradigm that expects immune responses to non-self because "The immune system evolved to discriminate infectious nonself from noninfectious self" 24 , but they support the danger model of Polly Matzinger, who argues that "the immune system is more concerned with entities that do damage than with those that are foreign" 25 .…”

Self-DNA Early Exposure in Cultivated and Weedy Setaria Triggers ROS Degradation Signaling Pathways and Root Growth Inhibition

“…Accordingly, S. pumila DNA at 10 ng/µL, besides inhibiting conspecific seedlings, also showed a marginal inhibitory effect on congeneric ( S. italica ) seedlings, although in this latter case, the treatment vs. control comparison produced a borderline p -value. Therefore, in the context of species-specific biological control, our study highlights the promising role of S. pumila DNA as a potential species-specific weedicide in analogy to its previously suggested use as a species-specific pesticide [ 10 , 29 , 30 , 31 ]. However, upscaling tests in an open field are obviously required in order to clarify the persistence of extracellular DNA and the reliability of its self-inhibitory effects under more realistic conditions, as well as the possible interference with cultivations of phylogenetically related crops.…”