Issue Information

Abstract

Neutrophils represent the largest population of white blood cells in the body. They play critical roles in antimicrobial defenses. When neutrophils encounter clusters of bacteria or fungi, an autocatalytic release of LTB4 and other mediators by the neutrophils arriving at the sites of infection drives the exponentially fast recruitment of more neutrophils to the site. The process, known as swarming, is a key for sealing off sites of infection and protecting healthy tissues. Methods: New technologies developed in our lab enable us to study thousands of neutrophil swarms at once and gain a new understanding of human and mouse neutrophil activities at the cellular and molecular level. Results: We tested the swarming of human neutrophils on patterned live fungi and bacteria. In control experiments, Staphylococcus aureus colonies doubled their size within 1 hour, and Candida albicans started growing in 3 hours. When incubated with human neutrophils, large swarms formed on top of the microbe clusters. Neutrophils vigorously swarmed against S. aureus and delayed its growth by up to 12 hours. Neutrophils also swarmed against C. albicans delayed the growth of hyphae for up to 16 hours. Disruption of swarming mediators compromised the ability of neutrophils to swarm and limited the ability to contain S. aureus and C. albicans. Neutrophil extracellular traps were formed during neutrophil swarming against C. albicans and disruption of NETs and ROS production compromised swarming control of the fungi. Conclusion: Swarming is an important mechanism of controlling bacteria and fungi growth in clusters that warrants further investigation.