Adenosine-A sub(3) receptors in neutrophil microdomains promote the formation of bacteria-tethering cytonemes

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