Neural representation of cytokines by vagal sensory neurons

The nervous system coordinates with the immune system to detect and respond to harmful stimuli. Inflammation is a universal response to injury and infection that involves the release of cytokines. While it is known that information about cytokines is transmitted from the body to the brain, how the nervous system encodes specific cytokines in the form of neural activity is not well understood. Using in vivo calcium imaging, we show that vagal sensory neurons within the nodose ganglia exhibit distinct real-time neuronal responses to inflammatory cytokines. Some neurons respond selectively to individual cytokines, while others encode multiple cytokines with distinct activity patterns. In a mouse model of colitis, inflammation increased the baseline activity of these neurons but decreased responsiveness to specific cytokines, reflecting altered neural excitability. Transcriptomic analysis of vagal ganglia from colitis mice revealed downregulation of cytokine signaling pathways, while neuronal activity pathways were upregulated. Thus, nodose ganglia neurons perform real-time encoding of cytokines at the first neural station in a body-brain axis, providing a new framework for studying the dynamic nature of neuroimmune communication. Overall design: Bulk RNA-seq was performed on dissociated vagal ganglia from adult C57BL/6J mice (2–8 months old) given 4% DSS in drinking water for 7 days to induce colitis, compared to untreated controls. Left and right vagal ganglia were harvested on day 7 or 8, enzymatically dissociated, and purified cell suspensions were flash-frozen and submitted to Singulomics Corporation (Bronx, NY) for RNA extraction, library preparation and sequencing