Neutrophils as chameleons of tissue inflammation and host-pathogen interactions

Neutrophils are acute responders to bacterial and fungal infection; however, their roles in disease extend far beyond their critical roles in countering pathogens. In this review, we seek to provide some broader context based on recent literature that highlights the contributions of the neutrophil lineage to cancer and chronic inflammation. Their importance for immunomodulation is underscored by their capacity to generate cytokines and chemokines, reactive oxygen species, granule secretory proteins, and use regulated inflammatory cell death pathways for the release of neutrophil extracellular traps. The potential to alter the balance between circumscribed inflammation and collateral tissue damage is most notable when considering the diverse contents and functions of secretory vesicles, and tertiary, specific, and azurophilic granules. We still have much to learn about the generation of granules in neutrophil progenitors, the factors controlling their release from mature neutrophils, and the cellular consequences for misfolding, misplacement, and premature release of granule contents from neutrophils. This review discusses recent advances in our understanding of neutrophil biology, roles in disease, and opportunities for depletion, inhibition, or supplementation and restoration of function.