Regulation of Germ Cell Apoptosis by Innate Immune Pathways in Caenorhabditis elegans Exposed to Ionizing Radiation

Ionizing radiation induces cytokine expression, affecting apoptosis through pro- and anti-apoptotic signals. Although some innate immune pathways regulating radiation-induced germ cell apoptosis have been identified in Caenorhabditis elegans, the precise mechanisms remain unclear. To clarify how innate immune genes regulate germ cell apoptosis, we first combined transcriptome sequencing and WormExp enrichment analysis to explore early gene expression changes in C. elegans after irradiation. The results showed that radiation triggers innate immunity genes similarly to pathogen responses. Subsequently, we employed mutants of innate immune pathways to investigate the underlying regulatory mechanisms. Germ cell apoptosis was reduced in pmk-1(km25), mpk-1(n2521), dbl-1(wk70), and daf-2(e1370) innate immunity related-mutants compared to N2 worms after irradiation. RNA-seq analysis revealed that the innate immune gene expression was downregulated in the mutant pmk-1(km25), while upregulated in mpk-1(n2521), dbl-1(wk70), kgb-1(um3), and daf-2(e1370). Pro-apoptotic genes egl-1 and ced-13 were significantly upregulated in wild-type worms and these mutants postirradiation. Further RNA-seq enrichment analysis using Gene Set Enrichment Analysis (GSEA) indicated distinct biological processes in these mutants after irradiation. Genes upregulated in wild-type but downregulated in mutants were involved in innate immunity, and RNAi of dod-21 significantly inhibited germ cell apoptosis. This suggests that reduced apoptosis in mutants is partly due to decreased expression of innate immunity genes.