Migration of neutrophils from inflamed skin occurs following microbial but not sterile inflammation and contributes to lymphocyte proliferation

Neutrophils are the first leukocytes to migrate from the bloodstream to the site of infection or injury. They possess a plethora of pathogen-killing mechanisms including phagocytosis, ROS production, NETosis and degranulation. Due to their crucial role in host defence, patients with defects in neutrophil number and function are highly susceptible to bacterial and fungal infections. On the other hand, activation of neutrophils is also associated with the tissue damage seen in some sterile inflammatory diseases. In vivo, it is thought that neutrophils are short-lived cells that die at inflammatory foci.In this study we used transgenic mice expressing the optical highlighters Kikume and Kaede to compare the fates of neutrophils recruited to different types of inflammation in the ear. In our models of sterile inflammation, a scratch with a needle or contact with a cauterising iron failed to induce neutrophil migration from the skin to the draining lymph node. In contrast, a very small number of neutrophils were found to egress from an LLC tumour to the draining lymph node. This, in turn, contrasts with our model of microbial inflammation, using inactivated S. aureus, wherein we observed a large number of neutrophils migrating from the site of injury to the draining lymph node. Additionally, neutrophils recruited to microbial lesions were more activated than neutrophils recruited to sterile injuries. Following an intradermal injection of S. aureus neutrophils were the main cell type to migrate from the skin to the draining lymph node. Subsequent experiments revealed that this migration promoted T cell, but not B cell, proliferation in the draining lymph node, suggesting that neutrophils may interact with the adaptive immune system.In conclusion we show that neutrophils can display differences in phenotype and fate in vivo that are dependent upon the type of inflammatory injury, and that neutrophil egress of infectious lesions may promote T cell responses