Roles of transcription factors and chromatin remodelers in regulating innate immune responses in <i>Caenorhabditis elegans</i>

SUMMARY Effective immunity requires the ability to mount strong pathogen defenses while minimizing detrimental effects on organismal fitness. To achieve this balance, many immune genes are maintained in a transcriptionally repressed but responsive state, ensuring rapid induction upon infection and timely repression once the threat subsides. This dynamic regulation is controlled by transcription factors and chromatin remodelers that fine-tune the accessibility of immune loci. The nematode Caenorhabditis elegans provides a powerful model for dissecting these mechanisms in non-professional immune cells. Its antiviral RNA interference (RNAi) pathway serves as a rapid, sequence-specific silencing system targeting viral RNA. Complementing RNAi, the intracellular pathogen response represents a specialized, inducible transcriptional program that protects C. elegans from intracellular pathogens, including viruses and microsporidia. In addition, pathways regulated by STAT family transcription factors coordinate immune activation in a pathogen- and tissue-specific manner, providing further regulatory diversity. This review explores how transcriptional and chromatin mechanisms coordinate these distinct immune programs to maintain effective yet balanced immune responses. Investigating these pathways in C. elegans continues to uncover both conserved and novel principles of immune regulation, offering insight into how organisms integrate transcriptional control with physiological constraints to thrive in a pathogen-rich environment.