Abstract
Neutrophils move from the blood into tissues, migrate under the guidance of chemical gradients, and accumulate at sites of infection, where they phagocytose and kill microbes within minutes. These processes have been considered the keystone of innate immune responses for more than five decades. However, it appears that these processes accurately describe only the situation when neutrophils encounter small numbers of disparate microbes. Recent observations revealed that when neutrophils encounter large fungi or clusters of bacteria that are too large for individual neutrophils to kill, one more process, known as swarming, is needed. During this process, the first neutrophils that reach the microbial target release leukotrienes and other molecules that stimulate more neutrophils in the vicinity to converge on the same target. A chain reaction ensues between the leukotrienes guiding the neutrophils toward the swarm and the attracted neutrophils releasing more leukotrienes. This chain reaction empowers multiple neutrophils to coordinate their activities, drives the explosively-fast accumulation of neutrophils, and enables neutrophils to neutralize large microbes and clusters of microbes, which would otherwise be outside the neutrophils reach. The molecular and cellular details of this chain reaction and the mechanisms that stop the chain reaction from damaging healthy tissues are just beginning to emerge, enabled by innovative, engineered tools.