Modulating neutrophils leads to changes in CNS output

It has become increasingly evident that immune cells play a role in modulating brain function. Neutrophils are the most abundant innate immune cell in mammals. Until recently, our understanding of the physiological role of these cells was limited to infection and cancer. Recently, it has emerged that neutrophils play critical roles in modulating tissue health and physiology. There has been evidence that neutrophils populate the rodent meninges. As such, we hypothesized that like other meningeal immune cells, neutrophils play a neuromodulatory role. Using a depletion paradigm, anti-Ly6G antibody injection, we demonstrate that the loss of neutrophils leads to changes in cognitive flexibility and social interactions in mice. Furthermore, the depletion paradigm led to a 50% decrease in the number of neutrophils in the meninges, which in turn led to the proliferation of resident immature neutrophils within the meninges. Finally, our data show that this immature population reenters the cell cycle only in response to specific physiological stimuli (neutrophil depletion, and stress). In conclusion, this study demonstrates that there are resident neutrophils within the meninges and that elucidating their function in the nervous system will deepen our understanding of immune regulation of brain function.