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Abstract
The A3-adenosine receptor (A3AR) has recently emerged as a key regulator of neutrophil behaviour. Using a fluorescent A3AR ligand, we show that A3ARs aggregate in highly polarized immunomodulatory microdomains on human neutrophil membranes. In addition to regulating chemotaxis, A3ARs 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 A3AR agonist stimulates the formation of these projections and bacterial phagocytosis, whereas an A3AR-selective antagonist inhibits cytoneme formation. Our results shed new light on the behaviour of neutrophils and identify the A3AR as a potential target for modulating their function.
Highlights
Extracellular nucleotides/nucleosides are critical mediators of immune cell function [1]
We found that endogenous A3-adenosine receptor (A3AR) aggregate into plaque-like microdomains on human neutrophil membranes
We investigated the localization and role of endogenous A3ARs in living human neutrophils using the recently developed fluorescent A3AR ligand CA200645, a xanthine amine congener derivative connected via a linker to a BODIPY 630/650 fluorophore [10]
Summary
Extracellular nucleotides/nucleosides are critical mediators of immune cell function [1]. We demonstrate the involvement of A3ARs in the formation of these structures, which enable neutrophils to sample, capture and ‘reel in’ pathogens for phagocytosis.
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