Neutrophil swarming: an essential process of the neutrophil tissue response

Abstract

Neutrophil infiltration into inflamed and infected tissues is a fundamental process of the innate immune response. While neutrophil interactions with the blood vessel wall have been intensely studied over the last decades, neutrophil dynamics beyond the vasculature have for a long time remained poorly investigated. Recent intravital microscopy studies of neutrophil populations directly at the site of tissue damage or microbial invasion have changed our perspective on neutrophil responses within tissues. Swarm-like migration patterns of neutrophils, referred to as 'neutrophil swarming', have been detected in diverse tissues under conditions of sterile inflammation and infection with various pathogens, including bacteria, fungi, and parasites. Current work has begun to unravel the molecular pathways choreographing the sequential phases of highly coordinated chemotaxis followed by neutrophil accumulation and the formation of substantial neutrophil clusters. It is now clear that intercellular communication among neutrophils amplifies their recruitment in a feed-forward manner, which provides them with a level of self-organization during neutrophil swarming. This review will summarize recent developments and current concepts on neutrophil swarming, an important process of the neutrophil tissue response with a critical role in maintaining the balance between host protection and inflammation-driven tissue destruction.

Missing in action—The meaning of cell death in tissue damage and inflammation

“…It is yet not clear which factors released by dying cells attract further neutrophils and induce swarming and clustering. ATP was suggested as one of these attracting molecules . Interestingly, we observed ATP to also augment aggNET formation .…”

“…During the last years, the technological progress in two‐photon intravital microscopy has enabled observation of neutrophils in vivo over extended periods of time. By this means, a remarkable neutrophil behavior was discovered that is reminiscent of the swarming of insects and is therefore referred to as neutrophil swarming . At sites of tissue injury or infection, groups of neutrophils undergo highly coordinated series of movements, followed by cell accumulation and clustering .…”

Aggregated neutrophil extracellular traps resolve inflammation by proteolysis of cytokines and chemokines and protection from antiproteases

“…During the last few years, the technological progress in 2-photon intravital microscopy has enabled the discovery of neutrophil swarming, a phenomenon characterized by highly coordinated series of neutrophil movement, followed by cell accumulation mediated by chemoattractant signals and adhesion molecules (46). Swarming is observed during infection and sterile inflammation in both mouse and human neutrophils (47). Interestingly, cell death, both in the inflamed surrounding tissue and within the neutrophil cluster itself, seems to amplify swarming.…”

Integrative Physiology of Pneumonia

“…Neutrophils produce the neutrophil-attracting and -activating chemokine CXCL2, and neutrophilic production of CXCL2 can drive a self-amplifying feed-forward loop of localized neutrophilia that is important to defense but also a contributor to lethal lung injury (51). Neutrophil production of chemokines like CXCL10 and CXCL2 may contribute to "swarming" behavior of neutrophils (253), in which neutrophil activation amplifies the local recruitment of neutrophils within the air spaces of infected lungs (FIGURE 3). In some cases, neutrophils also can be a source of IL-17 (60,533), a cytokine driving protective immunity through the induction of CXCL5, CXCL1, G-CSF, and enhanced phagocytic antimicrobial defense (69,559).…”