Toll-like receptor signaling in neurons modulates C. elegans feeding behavior in a hunger state-dependent manner.

Abstract

Animals face the risk of encountering pathogenic microbes while foraging for resources. Assessing the risk of nutrition vs. infection can result in the behavioral regulation of immune processes. Behavioral immunity in the nematode roundworm Caenorhabditis elegans (C. elegans) is regulated, in part, by the innate immune molecule TOL-1: a homolog of vertebrate Toll-like Receptor (TLR) proteins that influences C. elegans pathogen avoidance behaviors by promoting the development of CO₂-detecting chemosensory neurons. While TOL-1's role in pathogen avoidance is well established, its role in an opposing behavior - foraging - has not been examined. In addition to pathogenic bacteria, preferred food for C. elegans, such as Escherichia coli (E. coli), create significant and aversive environmental CO₂ levels which may limit feeding behaviors in a tol-1 dependent manner. We have found that in addition to conferring antibacterial immunity, TOL-1 signals in neurons through the p38 MAPK PMK-1 to promote turning behavior and limit foraging when food is abundant and that the anorectic TOL-1/PMK-1 pathway is attenuated during starvation to promote foraging. These data highlight the dynamic role of a conserved innate immune cascade in neurons during both high and low hunger states and identify mechanisms underlying the neuro-immune control of feeding strategies.