Trends in Immunology
Feature ReviewSpecial Issue: New Advances in Neutrophil ImmunityThe Neutrophil Life Cycle
Section snippets
The Neutrophil as a Double-Edged Sword in Health and Disease
Neutrophils (also named polymorphonuclear leukocytes) are phagocytes with an essential role in defending the host against invading pathogens, particularly bacteria and fungi 1., 2.. The killing of these organisms in phagosomes is mediated by: (i) fusion with lysosomes (granules) liberating cytotoxic proteins, peptides, and enzymes into the phagolysosome [3]; and (ii) activation of a membrane-bound NADPH-oxidase producing superoxide anions (O2–) that in turn, are metabolized into hydrogen
The Mammalian Mitotic Neutrophil Pool
The neutrophil originates from myeloid lineage progenitor cells (common myeloid progenitors, CMPs) located within the bone marrow and extramedullary tissues, including the spleen. During the initial differentiation steps, the myeloid progenitors (myeloblasts) retain their propensity to differentiate into both the monocyte/macrophage lineage and the neutrophil lineage, as well as the other myeloid cells, namely, eosinophils and basophils. This common differentiation ends with the last
Intravascular Neutrophil Pools
Mature neutrophils are present in the vasculature in two pools: a free-flowing intravascular blood pool and a blood pool residing in certain tissues. This latter pool is generally referred to as the ‘marginated pool’. Early studies suggested that marginated neutrophils were in complete equilibrium with free-flowing cells and, therefore neutrophils from either pool were indistinguishable [52]. The major sites for marginated neutrophils in humans are the liver, spleen and bone marrow itself [53],
Neutrophil Dynamics in Blood and Tissues
Mouse and human neutrophils that are newly released into the bloodstream are endowed with distinct phenotypic properties in that they gradually change over time following circadian oscillations [76]. Moreover, at least in the mouse, these phenotypic changes parallel changes in their transcriptional and migratory properties of neutrophils 76., 77. (Figure 2, Key Figure). A major functional pathway affected by circadian rhythms is the rearrangement of the actin cytoskeleton over time, leading to
Concluding Remarks
The variety of kinetics and functions described for neutrophils is consistent with the emerging view that these cells are multifaceted. At least part of the neutrophil pool is essential in host defense against invading microorganisms and is crucial for a successful immune response. On the negative side, neutrophils are involved in the pathogenesis of a plethora of inflammatory diseases and can, in certain instances, suppress antitumor responses. Thus, it is clear that neutrophils may become
Clinician’s Corner
Neutrophils are among the principal effectors of the innate immune response and are instrumental in the first line of defense against invading microbes.
While there may be important differences between human neutrophils and those of other mammalian species, much has been learned from studies in transgenic animal models.
The production, circulation, and clearance of neutrophils is altered by inflammatory stimuli, such as those encountered in acute conditions, such as bacteremia, and chronic
Outstanding Questions
What are the real transit times of neutrophils in blood, bone marrow, and tissues? These times may provide insights into the non-immune roles and pathogenic potential of neutrophils in tissues.
What is the evolutionary basis for the diurnal behavior of neutrophils? Gating antimicrobial functions or protecting the tissues of the host are possible benefits of this behavior.
What are the mechanisms of neutrophil clearance in mice and humans? In which tissues does clearance occur? Understanding such
Acknowledgments
The work in the authors laboratories is funded by (ERC) Medical Research Council, Wellcome Trust, GlaxoSmithKline, MedImmune, the NIHR Cambridge Biomedical Research Centre, British Heart Foundation, National Institute for Health, Cambridge NIHR Biomedical Research Centre, the MCIU (Ministerio de Ciencia, Innovación y Universidades), the Pro-CNIC Foundation, the Dutch Science Agenda (NWA) and the Netherlands Organization for Scientific Research (NWO). The CNIC is a Severo Ochoa Center of
Glossary
- Chédiak–Higashi syndrome
- caused by deficiency in a gene required for lysosomal trafficking and phagocytosis that results in immune deficiency and albinism.
- Chronic granulomatous disease (CGD)
- immunodeficiency characterized by mutations in genes needed for the generation of ROS in granulocytes.
- Common myeloid progenitors (CMPs)
- type of hematopoietic progenitors that give rise to all myeloid-lineage cells in adult hematopoiesis.
- Compensatory anti-inflammatory response syndrome (CARS)
- comprises a period
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