Role of the Nervous System in the Control of Proteostasis during Innate Immune Activation: Insights from C. elegans

Like other free-living nematodes, the one-millimeter-long nematode Caenorhabditis elegans lives in soils and composts rich in microorganisms, including human microbial pathogens. In the laboratory, C. elegans animals are typically propagated by feeding them Escherichia coli. This bacterium is effectively disrupted by the C. elegans pharyngeal grinder and essentially no intact bacterial cells can be found in the intestinal lumen of healthy, young animals. Once in the gut, however, pathogenic bacteria are capable of proliferating, invading host cells, and killing C. elegans by infectious processes. Bacterial pathogens can also adhere to the cuticle of the nematode, causing a defensive swelling response of the epidermal cells. While C. elegans lacks adaptive immunity, it responds to pathogen exposure by avoiding certain potentially pathogenic bacteria and by activating an inducible innate immune system. Thus, pathogen avoidance, grinding, swelling, peristalsis, and secretion of antimicrobial substances prevent microbial colonization of C. elegans by bacterial pathogens. Increasing evidence highlights the role of the C. elegans nervous system in the control of some of these immune responses against bacterial pathogens.