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Neutrophil migration in infection and wound repair: going forward in reverse
Sofia de Oliveira1*, Emily E.Rosowski1* and Anna Huttenlocher1,2
Abstract | Neutrophil migration and its role during inflammation has been the focus of increased interest in the past decade. Advances in live imaging and the use of new model systems have helped to uncover the behaviour of neutrophils in injured and infected tissues. Although neutrophils were considered to be short-lived effector cells that undergo apoptosis in damaged tissues, recent evidence suggests that neutrophil behaviour is more complex and, in some settings, neutrophils might leave sites of tissue injury and migrate back into the vasculature. The role of reverse migration and its contribution to resolution of inflammation remains unclear. In this Review, we discuss the different cues within tissues that mediate neutrophil forward and reverse migration in response to injury or infection and the implications of these mechanisms to human disease.
Neutrophils are the most abundant leukocytes in the blood, and they lead the first wave of host defence against infection or tissue damage. Neutrophils are power ful effector cells that destroy infectious threats through phagocytosis, degranulation, reactive oxygen species (ROS) and neutrophil extracellular traps13. Neutrophil loss due to disease or therapy-induced side effects has devastating consequences that are characterized by recurrent severe infections. However, excess infiltration and activation of neutrophils at a site of tissue damage can cause chronic inflammation, limit injury repair and lead to loss of organ function1,4. Neutrophils mediate tissue damage through the release of cytokines, proteases and other factors contained in their cytoplasmic granules and also by regulating the activity of the adaptive immune response, including both B cell and Tcell activation. Therefore, the migration and activation of neutrophils must be finely controlled. Recent advances in invivo imaging techniques and new invitro systems incorporating micro-fluidics and three-dimensional models have enabled researchers to directly visualize and quantify neutrophil behaviour (BOX1). These developments have spawned more complex studies regarding the role of neutrophils in the context of tissue homeostasis and disease, including wound healing, chronic inflammation, infection and cancer. As the role of neutrophils as key modulators of the immune response becomes clearer, it is becoming more important to understand neutrophil migration in the context of...