Distinct Roles of Sensory Neurons in Mediating Pathogen Avoidance and Neuropeptide-Dependent Immune Regulation

Increasing evidence implies an extensive and universal interaction between the immune system and the nervous system. Previous studies showed that OCTR-1, a neuronal G-protein-coupled receptor (GPCR) analogous to human norepinephrine receptors, functions in sensory neurons to control the gene expression of both microbial killing pathways and the unfolded protein response (UPR) in Caenorhabditis elegans. Here, we found that OCTR-1-expressing neurons, ASH, are involved in controlling innate immune pathways. In contrast, another group of OCTR-1-expressing neurons, ASI, was shown to promote pathogen avoidance behavior. We also identified neuropeptide NLP-20 and AIA interneurons, which are responsible for the integration of conflicting cues and behaviors, as downstream components of the ASH/ASI neural circuit. These findings provide insights into a neuronal network involved in regulating pathogen defense mechanisms in C. elegans and might have broad implications for the strategies utilized by metazoans to balance the energy-costly immune activation and behavioral response. Cao et al. show that chemosensory neurons have the ability to coordinate behavioral and immune responses upon bacterial infections in C. elegans. The underlying mechanisms involve interneurons and neuropeptide signaling and provide insights into tactics that may be used by animals when dealing with pathogen threats.