Detection of Pathogens and Regulation of Immunity by the Caenorhabditis elegans Nervous System

Abstract

Although Caenorhabditis elegans has been used as a model host for studying host-pathogen interactions for more than 20 years, the mechanisms by which it identifies pathogens are not well understood. This is largely due to its lack of most known pattern recognition receptors (PRRs) that recognize pathogen-derived molecules. Recent behavioral research in C. elegans indicates that its nervous system plays a major role in microbe sensing. With the increasing integration of neurobiology in immunological research, future studies may find that neuronal detection of pathogens is an integral part of C. elegans-pathogen interactions. Similar to that of mammals, the C. elegans nervous system regulates its immune system to maintain immunological homeostasis. Studies in the nematode have revealed unprecedented details regarding the molecules, cells, and signaling pathways involved in neural regulation of immunity. Notably, some of the studies indicate that some neuroimmune regulatory circuits need not be "activated" by pathogen infection because they are tonically active and that there could be a predetermined set point for internal immunity, around which the nervous system adjusts immune responses to internal or external environmental changes. Here, we review recent progress on the roles of the C. elegans nervous system in pathogen detection and immune regulation. Because of its advantageous characteristics, we expect that the C. elegans model will be critical for deciphering complex neuroimmune signaling mechanisms that integrate and process multiple sensory cues.

Keywords: Caenorhabditis elegans; G protein-coupled receptor; innate immunity; neural regulation; neurotransmitter; pathogen recognition; the nervous system.

FIG 1

A paradigm of pathogen recognition by C. elegans. Pathogens are detected by either the immune system, the nervous system, or both, which then triggers the innate immune response and/or behavioral responses. Novel pathogens or pathogens that escape detection likely cause infection and disturbance in cellular homeostasis, which subsequently activate immunity and/or behavioral changes. Such infections and disturbances would also signal to the nervous system and trigger learning responses so that the nematode would recognize the same pathogens during a second encounter.