Neutrophils at the crossroads of innate and adaptive immunity

Abstract

Neutrophils are the most abundant leukocytes in blood. From the circulation, they are quickly mobilized to sites of inflammation and/or infection. At the affected tissues, neutrophils display an impressive array of antimicrobial functions, including degranulation, production of reactive oxygen species (ROS), phagocytosis, and formation of neutrophil extracellular traps (NET). Because neutrophils are the first type of leukocytes to arrive at affected tissues and display potent microbicidal functions, they have been classically viewed as the first line of defense. In this view, neutrophils only destroy invading pathogens and then quietly die at the site of infection. However, in the last decade it has become increasingly evident that neutrophils are much more complex cells having not only effector functions in the innate immune response, but also the capacity of modulating the adaptive immune response, via direct interaction with, or by producing cytokines that affect dendritic cells and lymphocytes. In addition, neutrophil heterogeneity with clear different functional phenotypes has been recently described particularly in cancer and inflammation. This review provides an overview on the life of a neutrophil describing its beginnings, lifespan, and their principal functions in innate and adaptive immunity. Also, neutrophil heterogeneity and our current understanding of neutrophil contributions to health and disease are discussed.

What Is the Evolutionary Fingerprint in Neutrophil Granulocytes?

“…The rates by which certain pathogens are ingested may vary between species [163], but the principle remains the same. The neutrophil engulfs a pathogen into a phagosome, which then fuses with vesicles from the endoplasmic reticulum and Golgi complex, as well as with lysosomes to build the phagolysosome [161,164]. Microbes are then intended to be killed in oxygen-dependent and -independent ways.…”

“…The microbicidal components split the pathogen enzymatically, but also reactive oxygen species (ROS) are involved [153]. Phagocytosis is mediated by receptors, as pathogens are recognized through either opsonins, antibodies, or pathogen-associated molecular patterns [161,165].…”

“…Hence, the principles of this are summarized with the human example. The release of granules needs tight control to prevent cytotoxic effects of the components where not desired [161]. First, secretory vesicles are released to enable adhesion.…”

“…Dying granulocytes are furthermore cleared in the bone marrow, liver, and spleen. An additional exit way from the circulating blood is towards the environment via urine, oral mucosa, the ocular surface, or pus [161]. Purulent lesions in mammals differ enormously from the ones in birds and reptiles, even macroscopically.…”

Analysis of Spatial Organization of Suppressive Myeloid Cells and Effector T Cells in Colorectal Cancer—A Potential Tool for Discovering Prognostic Biomarkers in Clinical Research

“…In fact, tumor associated neutrophils are very heterogeneous cell population with several pro-and anti-tumor functions (24). They can engage with different tumor resident immune cell types performing either stimulatory or inhibitory functions (25). Our findings suggest that tumors with lower distance between granulocytic myeloid cells and cytotoxic T cells may have higher CD4 + memory T cell content.…”