Neutrophil Functions in Host Immunity, Inflammation and Tissue Repair

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Background

Neutrophils are specialized immune cells that represent a first cellular line of defense against bacterial and fungal infections, as well as performing key roles in the inflammatory response. Conserved in all vertebrates, the short-lived neutrophils are the most abundant circulating leukocytes in humans. Upon stimulation, circulating neutrophils leave the bloodstream to travel to sites of infection or sterile inflammation, where they internalize and kill pathogens, utilizing an arsenal of highly toxic chemicals including reactive oxygen species, antimicrobial peptides, and powerful proteases.

Compared with lymphocytes, and some other innate immune cells, such as macrophages, neutrophils have remained relatively underappreciated in homeostasis and disease. Until not so long ago, neutrophils were seen as rather unsophisticated cells that generate excess inflammation, killing other cells indiscriminately. This view likely arose because, although it is relatively easy to prepare a large number of neutrophils from blood or bone marrow, performing research is limited by their relatively short lifespan, inaccessibility to being cultured or genetically modified, and the ease with which they are activated. Thus, alternative cellular models offering better tractability were frequently substituted for in vitro studies. Even in vivo functions performed by neutrophils may have been ascribed to other cells such as macrophages that were longer lived and were identified in biopsies.

With the advent of genetically accessible model organisms, as well as the emergence of new technologies and in vitro systems, this view is changing. Increased complexity of neutrophil biology is beginning to be appreciated. Rather than being indiscriminate killers, neutrophils are emerging as nuanced players in host defense, disease progression, and regeneration. It has become apparent that neutrophils are not transcriptionally silent as had long been assumed. Neutrophil extracellular traps and neutrophil subsets have emerged as fashionable, and highly controversial topics. Neutrophils are involved in, and indeed direct cross-talk with other leukocytes, be it interactions with platelets for improved extravasation, cross-talk with the adaptive immunity to direct efficient immune responses, or sending find-me and eat-me signals to macrophages to direct the resolution of inflammation. As new roles in tissue development, homeostasis, regeneration, disease progression (for instance of cancer and chronic inflammation) are beginning to emerge, it is clear that many facets of neutrophil biology remain to be fully elucidated.

In this Research Topic, we welcome contributions as Original Research, Case Reports, Methods, Reviews, Mini Reviews and Perspective articles covering the following topics:

1. Neutrophil migration to and interaction with immune stimuli
2. Neutrophil roles in directing the resolution of inflammation
3. Neutrophil functions in autoimmunity
4. Neutrophil cross-talk with adaptive immunity

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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