An organismal understanding of C. elegans innate immune responses, from pathogen recognition to multigenerational resistance

Abstract

The nematode Caenorhabditis elegans has been a model for studying infection since the early 2000s and many major discoveries have been made regarding its innate immune responses. C. elegans has been found to utilize some key conserved aspects of immune responses and signaling, but new interesting features of innate immunity have also been discovered in the organism that might have broader implications in higher eukaryotes such as mammals. Some of the distinctive features of C. elegans innate immunity involve the mechanisms this bacterivore uses to detect infection and mount specific immune responses to different pathogens, despite lacking putative orthologs of many important innate immune components, including cellular immunity, the inflammasome, complement, or melanization. Even when orthologs of known immune factors exist, there appears to be an absence of canonical functions, most notably the lack of pattern recognition by its sole Toll-like receptor. Instead, recent research suggests that C. elegans senses infection by specific pathogens through contextual information, including unique products produced by the pathogen or infection-induced disruption of host physiology, similar to the proposed detection of patterns of pathogenesis in mammalian systems. Interestingly, C. elegans can also transfer information of past infection to their progeny, providing robust protection for their offspring in face of persisting pathogens, in part through the RNAi pathway as well as potential new mechanisms that remain to be elucidated. Altogether, some of these strategies employed by C. elegans share key conceptual features with vertebrate adaptive immunity, as the animal can differentiate specific microbial features, as well as propagate a form of immune memory to their offspring.

Keywords: Adaptive immunity; Innate immunity; Intergenerational; Invertebrate; Pattern recognition; Patterns of pathogenesis; Transgenerational.

Figure 1.. Detection of patterns of pathogenesis and immune inheritance in C. elegans.

Upon infection, C. elegans detects pathogens through several mechanisms, including 1) infection-induced damage, 2) microbial secondary products, and 3) surveillance of core cellular processes through expanded gene families. These signals induce transcription of immune response genes in the parents and 4) confer immunity to their progeny. Image was generated with BioRender.