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

Many migrating cells pattern signalling molecules to support their accumulation in target tissues. During inflammation, neutrophils achieve rapid swarming at sites of injury or infection by generating spatiotemporal gradients of chemoattractants. Whether these self-generated behaviours can be re-programmed to change disease course is unclear. Here, we show that neutrophil chemoattractant patterning machinery is subject to transcriptional reprogramming after microbial experience, leading to enhanced swarming and control of infection at subsequent wound sites in zebrafish. Through in vitro assays, we demonstrate that "trained swarming phenotypes" are cell-intrinsic and independent of the nature of the microbial target. Furthermore, genetic enhancement of 5-lipoxygenase in neutrophils is sufficient to improve neutrophil swarming and resistance to wound infection. Through mathematical modelling, we demonstrate that neutrophil-intrinsic alterations in chemoattractant release are sufficient to recapitulate trained swarming in infection-experienced animals. Together, these data suggest new routes for reprogramming cell migration in disease settings, via manipulating their ability to shape chemoattractant landscapes.