It is now widely recognized that neutrophils are highly versatile and sophisticated cells that display de novo synthetic capacity and may greatly extend their lifespan. In addition, concepts such as ...“neutrophil heterogeneity” and “neutrophil plasticity” have started to emerge, implying that, under pathological conditions, neutrophils may differentiate into discrete subsets defined by distinct phenotypic and functional profiles. A number of studies have shown that neutrophils act as effectors in both innate and adaptive immunoregulatory networks. In fact, once recruited into inflamed tissues, neutrophils engage into complex bidirectional interactions with macrophages, natural killer, dendritic and mesenchymal stem cells, B and T lymphocytes, or platelets. As a result of this cross-talk, mediated either by contact-dependent mechanisms or cell-derived soluble factors, neutrophils and target cells reciprocally modulate their survival and activation status. Altogether, these novel aspects of neutrophil biology have shed new light not only on the potential complex roles that neutrophils play during inflammation and immune responses, but also in the pathogenesis of several inflammatory disorders including infection, autoimmunity, and cancer.
Polymorphonuclear neutrophils, besides their involvement in primary defense against infections - mainly through phagocytosis, generation of toxic molecules, release of enzymes, and formation of ...extracellular traps - are also becoming increasingly important for their contribution to the fine regulation in development of inflammatory and immune responses. These latter functions of neutrophils occur, in part, via their de novo production and release of a large variety of cytokines, including chemotactic cytokines (chemokines). Accordingly, the improvement in technologies for molecular and functional cell analysis, along with concomitant advances in cell purification techniques, have allowed the identification of a continuously growing list of neutrophil-derived cytokines, as well as the characterization of their biological implications in vitro and/or in vivo. This short review summarizes crucial concepts regarding the modalities of expression, release, and regulation of neutrophil-derived cytokines. It also highlights examples illustrating the potential implications of neutrophil-derived cytokines according to recent observations made in humans and/or in experimental animal models.
Neutrophils have long been viewed as the final effector cells of an acute inflammatory response, with a primary role in the clearance of extracellular pathogens. However, more recent evidence has ...extended the functions of these cells. The newly discovered repertoire of effector molecules in the neutrophil armamentarium includes a broad array of cytokines, extracellular traps and effector molecules of the humoral arm of the innate immune system. In addition, neutrophils are involved in the activation, regulation and effector functions of innate and adaptive immune cells. Accordingly, neutrophils have a crucial role in the pathogenesis of a broad range of diseases, including infections caused by intracellular pathogens, autoimmunity, chronic inflammation and cancer.
Highlights • Neutrophils represent a cellular source of chemokines. • Neutrophils recruit and activate, via chemokines, discrete leukocyte populations. • Neutrophils, in virtue of their capacity to ...recruit innate and adaptive immunity cells via chemokines, potentially orchestrate sophisticated immune responses. • Neutrophil-derived chemokines contribute to the pathogenesis of infectious and non-infectious diseases.
Summary
Recent findings have uncovered novel fascinating aspects of the biology of neutrophils, which ultimately attribute to these cells a broader role in inflammation and immunity. One aspect that ...is currently under intensive investigation is the notion of neutrophil ‘heterogeneity’. Studies examining neutrophils in a variety of acute and chronic inflammatory conditions report, in fact, the recovery of CD66b+ cells displaying neutrophil‐like morphology at different degrees of maturation/activation, able to exert either immunosuppressive or proinflammatory properties. These heterogeneous populations of mature and immature neutrophils are indicated with a variety of names, including ‘low density neutrophils (LDNs)’, ‘low density granulocytes (LDGs)’, ‘granulocytic‐myeloid derived suppressor cells (G‐MDSCs)’, and immunosuppressive neutrophils. However, due to the lack of discrete markers that can unequivocally allow their specific identification and isolation, the precise phenotype and function of all these presumably novel, neutrophil‐like, populations have not been correctly defined yet. Aim of this article is to summarize current knowledge on the mature and immature neutrophil populations described to date, featuring immunosuppressive or proinflammatory properties, often defined as ‘subsets’, as well as to critically discuss unresolved issues in the field.
Review focuses on the molecular mechanisms regulating the interactions between neutrophils and NK cells in the human and mouse system.
The immune system is equipped with a plethora of mechanisms that ...protect the host from the harmful effects of environmental insults. However, the traditional “hierarchical” view of the immune response, in which innate, “nonspecific” cells are first recruited to the site of damage, before the highly “specific”, adaptive immune response develops, has been questioned recently. First, the innate response is much more specific than recognized previously: indeed, each cell of the innate system is not only endowed with an ever‐expanding array of germ‐line‐encoded receptors, which differentiate between distinct insults, but also is modulated continuously by other leukocytes that concomitantly interact with and respond to that particular insult. The other reason is that the cells of the innate system are instrumental for the adaptive system to accomplish its function, as they can also modulate the activity of lymphocytes reciprocally during the entire course of the immune response. This complex pattern of interactions is illustrated by recent advances on the functions of PMNs, clearly showing that unexpectedly, these cells also contribute to the regulation of the host immune response by crosstalk with innate and adaptive leukocytes, including NK cells. Herein, given the peculiar role of neutrophils and NK cells in inflammation, clearance of pathogens/viral‐infected cells, and cancer immunosurveillance, we summarize the current knowledge about the mechanisms whereby neutrophils and NK cells interact and regulate the activities of one another, as well as discuss their potential implications involved in the pathogenesis of chronic, inflammatory pathologies, infections, and tumors.
Summary
An increasing body of literature supports a role for neutrophils as players in the orchestration of adaptive immunity. During acute and chronic inflammatory conditions, neutrophils rapidly ...migrate not only to sites of inflammation, but also to draining lymph nodes and spleen, where they engage bidirectional interactions with B‐ and T‐lymphocyte subsets. Accordingly, a relevant role of neutrophils in modulating B‐cell responses under homeostatic conditions has recently emerged. Moreover, specialized immunoregulatory properties towards B or T cells acquired by distinct neutrophil populations, originating under pathological conditions, have been consistently described. In this article, we summarize the most recent data from human studies and murine models on the ability of neutrophils to modulate adaptive immune responses under physiological and pathological conditions and the mechanisms behind these processes.
In this article, we summarize the most recent data from human studies and murine models on the ability of neutrophils to modulate B‐ and T‐cell responses under physiological and pathological conditions and the mechanisms behind these processes.
Summary
Polymorphonuclear neutrophils are no longer considered as a homogeneous population of terminally differentiated and short‐lived cells that belong to the innate immune system only. In fact, ...data from the past decades have uncovered that neutrophils exhibit large phenotypic heterogeneity and functional versatility that render them more plastic than previously thought. Hence, their precise role as effector cells in inflammation, in immune response and in other pathophysiological processes, including tumors, needs to be better evaluated. In such a complex scenario, common knowledge of the differentiation of neutrophils in bone marrow refers to lineage precursors, starting from the still poorly defined myeloblasts, and proceeding sequentially to promyelocytes, myelocytes, metamyelocytes, band cells, segmented neutrophils, and mature neutrophils, with each progenitor stage being more mature and better characterized. Thanks to the development and utilization of cutting‐edge technologies, novel information about neutrophil precursors at stages earlier than the promyelocytes, hence closer to the hematopoietic stem cells, is emerging. Accordingly, this review discusses the main findings related to the very early precursors of human neutrophils and provides our perspectives on human neutropoiesis.
Neutrophils are the first line of defense against bacteria and fungi and help combat parasites and viruses. They are necessary for mammalian life, and their failure to recover after myeloablation is ...fatal. Neutrophils are short-lived, effective killing machines. Their life span is significantly extended under infectious and inflammatory conditions. Neutrophils take their cues directly from the infectious organism, from tissue macrophages and other elements of the immune system. Here, we review how neutrophils traffic to sites of infection or tissue injury, how they trap and kill bacteria, how they shape innate and adaptive immune responses, and the pathophysiology of monogenic neutrophil disorders.
Recent studies have revealed that neutrophils exhibit an unsuspected heterogeneity. In this context, the term high-density neutrophils (HDNs) has recently gained ground to define nothing more than ...neutrophils displaying an unaltered normal density. Therefore, as discussed here, we argue that the HDNs term must be avoided, as it is confounding and scientifically inappropriate.
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