Neuroimmune Education of Monocyte Function in Disease

Situation-specific cues drive circulating monocytes to attain multiple functional states. Such plasticity is critical for immunity and homeostasis, however, little is understood about how the balance of different functional states of monocytes is regulated. In rodents, circulating monocytes comprise inflammatory Ly6Chi monocytes which are recruited to inflamed tissues and vascular patrolling Ly6Clo monocytes, important for maintaining endothelial health. Profound changes to monocyte phenotype occur during Toxoplasma gondii infection, in association with increases in serum glucocorticoids and interferon (IFN)γ. Thus, we hypothesised that these signals may regulate monocyte state and function. We show that intraperitoneal administration of the synthetic glucocorticoid dexamethasone (DEX) increases the proportion of circulating inflammatory Ly6Chi monocytes, but IFNγ causes no change. Additionally, ex vivo conditioning assays suggest that glucocorticoid treatment enhances the inflammatory potential of monocytes. Together, these data support an unexpected role for neuro-immune cross-talk in orchestrating effective innate immune responses, and suggest that synthetic glucocorticoids may have a novel role for regulating monocyte state and function.