Adenosine‐A 3 receptors in neutrophil microdomains promote the formation of bacteria‐tethering cytonemes

The A 3 ‐adenosine receptor (A 3 AR) has recently emerged as a key regulator of neutrophil behaviour. Using a fluorescent A 3 AR ligand, we show that A 3 ARs aggregate in highly polarized immunomodulatory microdomains on human neutrophil membranes. In addition to regulating chemotaxis, A 3 ARs promote the formation of filipodia‐like projections (cytonemes) that can extend up to 100 μm to tether and ‘reel in’ pathogens. Exposure to bacteria or an A 3 AR agonist stimulates the formation of these projections and bacterial phagocytosis, whereas an A 3 AR‐selective antagonist inhibits cytoneme formation. Our results shed new light on the behaviour of neutrophils and identify the A 3 AR as a potential target for modulating their function.