From head to tail it's a 2 way street for neuro-immune communication

Abstract

Animals need to be able to rapidly and effectively respond to changes in their external and internal environment. To achieve this the nervous and immune systems need to coordinate their responses, integrating multiple cues including presence of potential pathogens, and availability of food. In our recent study (1) we demonstrate that signaling by sensory neurons in the head using the classical neurotransmitter serotonin can negatively regulate the rectal epithelial immune response upon infection of C. elegans with the naturally occurring bacterial pathogen Microbacterium nematophilum (M. nematophilum). The complicated nature of the mammalian brain and immune system has made it difficult to identify the molecular mechanisms mediating these interactions. With its simple, well described, nervous system and a rapidly growing understanding of its immune system, C. elegans has emerged as an excellent model to study the mechanisms by which animals recognize pathogens and coordinate behavioral and cellular immune responses to infection.

Keywords: G proteins; immune response; infection; sensory neurons; serotonin.

Figure 1.

Neuronal signaling pathways that regulate C. elegans cellular immune responses. A number of molecules released from DCVs act non-autonomously to regulate the immune response. (A) Serotonin, synthesized by TPH-1, in ADF chemosensory neurons acts via SER-1 and SER-7 receptors to suppress the immune response to M. nematophilum infection. Serotonin acts, directly (i) or indirectly (ii), to regulate GOA-1 signaling in the rectal epithelium. Although SER-1 and SER-7 receptors are not expressed on rectal epithelial cells under standard conditions, it remains to be determined whether regulation of SER-1 and SER-7 expression by infection may allow serotonin to act directly on these cells (i). Alternatively serotonin may activate SER-1 and SER-7 expressed on neurons, which then release a signal to activate GOA-1 signaling in rectal epithelial cells (ii). GOA-1 signaling acts upstream of, or in parallel to, EGL-30 signaling to suppress the Dar phenotype and reduce pathogen clearance rates. (B) The octopamine receptor, OCTR-1, suppresses the immune response to infection with Pseudomonas aeruginosa and is required in ASH and ASI neurons to suppress PMK-1 signaling and the unfolded protein response in non-neuronal cells. (C) Release of INS-7 or DBL-1 from the DCVs of unidentified neurons regulate gene expression in the intestine and epithelial cells respectively to mediate antibacterial and antifungal resistance. In addition dopamine, released from DCVs protects animals from repeat infection by enteropathogenic E. Coli.