Serotonergic Chemosensory Neurons Modify the C. elegans Immune Response by Regulating G-Protein Signaling in Epithelial Cells

Abstract

The nervous and immune systems influence each other, allowing animals to rapidly protect themselves from changes in their internal and external environment. However, the complex nature of these systems in mammals makes it difficult to determine how neuronal signaling influences the immune response. Here we show that serotonin, synthesized in Caenorhabditis elegans chemosensory neurons, modulates the immune response. Serotonin released from these cells acts, directly or indirectly, to regulate G-protein signaling in epithelial cells. Signaling in these cells is required for the immune response to infection by the natural pathogen Microbacterium nematophilum. Here we show that serotonin signaling suppresses the innate immune response and limits the rate of pathogen clearance. We show that C. elegans uses classical neurotransmitters to alter the immune response. Serotonin released from sensory neurons may function to modify the immune system in response to changes in the animal's external environment such as the availability, or quality, of food.

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

“…Our worked defined at least SER-1 and SER-7 receptors as playing a role in modulating the epithelial immune response. 1 However, in the absence of infection, the reported expression for SER-1 and SER-7 places neither receptor in the rectal epithelium, suggesting that their action on the epithelium is likely to be indirect.…”

“…1 In Pseudomonas ingestion increases intracellular calcium, which then increases tph-1 transcription and the levels of serotonin in ADF. 9 This response is cell-autonomously regulated by the C. elegans homolog of calcium/calmodulin-dependent protein kinase II (CaMKII), UNC-43.…”

“…Our work has shown that exogenous serotonin suppresses the rectal epithelial immune response to infection with M. nematophilum, while reductions in serotonin synthesis results in an increased immune response. 1 In comparison, during Pseudomonas aeruginosa infections, loss of serotonin has no effect on cellular immunity, while mutations in the neuropeptide processing enzymes egl-3 and egl-21 result in enhanced pathogen resistance. 2,13 This is due to the action of the insulin-like neuropeptide INS-7, acting as a DAF-2 agonist to negatively regulate resistance to Pseudomonas infection (Fig.…”

“…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.…”

An Elongin-Cullin-SOCS Box Complex Regulates Stress-Induced Serotonergic Neuromodulation

“…Several stressors induce behavioral changes in C. elegans through well-described serotonergic neurons, including a pair of sensory neurons called ADF. Serotonin production in ADF modulates different downstream networks to generate behavioral responses to various environmental stimuli, such as pathogenic bacteria, presence of novel food, starvation, or heat (Sze et al, 2000, Zhang et al, 2005, Liang et al, 2006, Anderson et al, 2013, Song et al, 2013, Tatum et al, 2015, Lemieux et al, 2015, Jin et al, 2016). Collectively, these studies suggest that similar to mammals, the C. elegans serotonergic neurons respond to a range of stressors to modulate neural circuits underlying multiple behavioral outcomes.…”