Self-extinguishing relay waves enable homeostatic control of human neutrophil swarming.

Neutrophils collectively migrate to sites of injury and infection. How these swarms are coordinated to ensure the proper level of recruitment is unknown. Using an ex vivo model of infection, we show that human neutrophil swarming is organized by multiple pulsatile chemoattractant waves. These waves propagate through active relay in which stimulated neutrophils trigger their neighbors to release additional swarming cues. Unlike canonical active relays, we find these waves to be self-terminating, limiting the spatial range of cell recruitment. We identify an NADPH-oxidase-based negative feedback loop that is needed for this self-terminating behavior. We observe near-constant levels of neutrophil recruitment over a wide range of starting conditions, revealing surprising robustness in the swarming process. This homeostatic control is achieved by larger and more numerous swarming waves at lower cell densities. We link defective wave termination to a broken recruitment homeostat in the context of human chronic granulomatous disease. [Display omitted] • Neutrophil swarming is organized by pulsatile, self-extinguishing waves of LTB4 • NADPH-oxidase activation is critical for relay wave self-extinction • Neutrophils adjust the size and number of waves to homeostatically control recruitment • Chronic granulomatosis disease neutrophils generate undamped relay waves that do not extinguish Strickland et al. find that human neutrophils organize pulsatile, self-extinguishing waves of leukotriene B4 to ensure robust homeostatic recruitment. Self-extinguishing waves are dependent on the activity of NADPH oxidase, and deficiency in this pathway leads to a reduced ability to extinguish relay waves. [ABSTRACT FROM AUTHOR]