In form for a swarm: programmable neutrophil swarming impacts infection outcome

Migrating cells often pattern the distribution of chemoattractants to support their accumulation in target tissues. Neutrophil swarming represents a prominent example in which cells engage in coordinated paracrine chemoattractant signalling for rapid clustering at sites of injury or infection. Whether neutrophil swarming can be regeared to influence immune outcomes is unclear. Here, we show that neutrophil swarming is subject to reprogramming after microbial experience and amenable to genetic enhancement with measurable effects on infection outcome. We demonstrate that zebrafish larvae exposed to prior microbial experience are trained to be more resistant to subsequent wound infection. Through live imaging and chemical perturbations, we show that these training effects are in part attributed to changes in neutrophil swarming and associated gene expression signatures. Among the reprogrammed genes, genetic enhancement of 5-lipoxygenase is sufficient to maximise neutrophil swarming and improve infection outcome. Finally, through mathematical modelling, we demonstrate that alterations in attractant secretion, sensitivity of bacterial detection and stop signals predict kinetics of neutrophil swarming and bacterial clearance in trained animals. Together, these data suggest new routes for reprogramming cell accumulation and positioning in tissues, via manipulating their ability to shape chemoattractant landscapes.