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

Abstract

SUMMARY 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.

Microbial Colonization Activates an Immune Fight-and-Flight Response via Neuroendocrine Signaling

“…Neurosensory inputs are necessary for pathogen avoidance behavior (Cao et al, 2017;Chang et al, 2011;Pradel et al, 2007;Reddy et al, 2009;Styer et al, 2008); however, how animals integrate information to modulate neuroendocrine signaling pathways remains largely unknown. To test whether colonization and bloating of the intestinal lumen may modulate neuroendocrine signaling, we studied the gene expression of different components of neuroendocrine pathways that might influence the avoidance behavior, including the NPR-1/GPCR pathway (npr-1, flp-18, and flp-21) (Styer et al, 2008), the DAF-7/TGF-b pathway , and the serotonin biosynthesis pathway (Shivers et al, 2009).…”

Caenorhabditis eleganssensory neurons modulate pathogen specific responses via HLH-30/TFEB transcription factor and FSHR-1 GPCR axes of immunity

“…We have earlier shown that non cell autonomous control of immunity by the nervous system, during P. aeruginosa infection, impinges on p38 MAPK pathway and noncanonical UPR pathways (Sun et al, 2011;Cao et al, 2017). C. elegans has approximately 120 cholinergic neurons and these can activate wnt signalling in the intestine in response to infection by S. aureus (Irazoqui et al, 2008;Labed et al, 2018).…”

“…Sensory neurons utilize neurotransmitters for synaptic transmission and neuropeptides for synaptic, extra synaptic, and medium to long range communications. Recent studies indicate a broad role for neuropeptide like proteins in control of physiological responses (Li, 2008;Nässel and Winther, 2010) as well as flight response to pathogenic bacteria (Cao et al, 2017;Lee and Mylonakis, 2017). Since intestine, the site of proliferation of E. faecalis or P. aeruginosa, is not innervated, neuropeptides present a possible mode of communication.…”

Intra Strain Variation of the Effects of Gram-Negative ESKAPE Pathogens on Intestinal Colonization, Host Viability, and Host Response in the Model Organism Caenorhabditis elegans

“…Previous research has highlighted the importance of the neural network in pathogen avoidance (Cao et al, 2017). It has also indicated that C. elegans mutants with deficiencies in neuronal signaling show enhanced clearance rates of pathogenic bacteria after transfer to a non-pathogenic food source (Kawli and Tan, 2008).…”