Vagus nerve stimulation activates two distinct neuroimmune circuits converging in the spleen to protect mice from kidney injury

Significance The ability of vagus nerve stimulation to generate anti-inflammatory and tissue-protective effects has been known for some time. We have made use of cutting-edge tools to precisely map the neural circuits that contribute to beneficial effects of vagus nerve stimulation. Stimulation was specifically restricted to either the afferent or efferent neurons in the vagus nerve by genetically programming the appropriate cells to express a light-sensitive cation channel. We show that, while both afferent and efferent signals provide protection from kidney injury, afferent stimulation generates a sympathetic response that protects mice in the absence of efferent vagus signals. This provides an insight into the pathways of neuroimmune protection and potential therapeutics.