Traps and hyper inflammation – new ways that neutrophils promote or hinder survival

Abstract

SummaryFor a long time neutrophil granulocytes were considered simply as terminally differentiated cells with a limited life span and pathogen killing by phagocytosis and chemical toxicity being the sole mode of action. However, work during the last 10 years has started to change this view fundamentally. Modern understanding is that neutrophils have an enormous complexity of functions. This review discusses very recent findings on how neutrophils can control the spread of pathogens and mediate their killing by mechanisms such as formation of DNA nets, how they influence tumour growth and adaptive immune responses and how they manoeuvre inside the diverse compartments of the body. It will also describe how the normally protective functions of neutrophils can have deleterious consequences if they occur in an uncontrolled fashion. These exciting novel findings are likely to completely and permanently change our view of this central leucocyte population.

Neutrophils release extracellular DNA traps in response to exercise

“…However, despite extensive research efforts in recent years, the molecular pathways and the biological significance of this phenomenon are just beginning to emerge. It appears that-dependent on stimulus, location, milieu, and activation state-several distinct but partially overlapping signaling pathways exist that culminate in the formation of NETs for varying purposes (30,45). Recently, Paul Kubes and colleagues (49,59) uncovered an alternative, nonlytic and very rapid process of NET formation that does not require cell death, thereby enabling intravascular neutrophils to expel their decondensed nuclear contents without losing their chemotactic and phagocytic abilities.…”

“…There is increasing evidence that release of chromatin serves as an ancient and highly conserved strategy of host defense (9). It also appears that NETs evolved to interact at different stages of innate immune responses (30). In the vasculature, NETs recently emerged as being crucially important to accomplish bidirectional crosstalk between innate immunity and blood coagulation, a task that seems inevitable to protect hosts from non-self and altered-self, and has therefore been termed immunothrombosis (21).…”

“…Although there are clearly many facets of NETs that require further exploration, it is quite undisputed that appropriate functioning of NETs is an important facet of effective host defense. On the other hand, aberrant or unresolved release of NETs can correlate with disease severity, imposes an increased risk of thrombotic events, may contribute to vascular injury and tissue damage, and has been implicated in the etiology of autoimmunity (9,30). As complexes of self-DNA and neutrophil-derived granule proteins provide a source of autoantigens and have been identified as potent activators of dendritic cells, NETs just recently emerged as key players in atherogenesis (18,19) and in the development of diverse autoimmune diseases including systemic lupus erythematosus (SLE) (27), Table 2.…”

Role of the glucocorticoid‐induced leucine zipper gene in dexamethasone‐induced inhibition of mouse neutrophil migration via control of annexin A1 expression

“…Neutrophils are activated via 5 distinct phases: tethering, rolling, adhesion, crawling, and transmigration. The key molecules that promote adhesion and transendothelial migration of neutrophils are selectins, such as leukocyte function-associated antigen-1 (CD11a/CD11b) and Mac-1 (CD11b/CD18), which bind to their cognate ligands on the endothelium, and cytokines, such as IL-8 (19,20). Moreover, migration of neutrophils is regulated by chemokines via a process known as chemotaxis.…”

Depletion of Neutrophils Exacerbates the Early Inflammatory Immune Response in Lungs of Mice Infected withParacoccidioides brasiliensis

“…They participate as the first line of innate immunity and as effectors of adaptive immunity, contributing to the development of inflammatory reactions [1, 2]. These cells exert mechanisms of defense, such as phagocytosis [3, 4], intracellular, and extracellular pathogen destruction by chemical means [4, 5], neutrophil extracellular traps (NETs) formation [4, 6], and the production of numerous cytokines, chemokines, and growth factors [7, 8] used to defeat microbial pathogens [4, 9]. Furthermore, recent discoveries have suggested novel roles of neutrophils in a variety of immunological and inflammatory aspects such as immunity against intracellular pathogens (viruses and intracellular bacteria), shaping of adaptive immunity at different levels, and new potential roles for NETs beyond antimicrobial functions [2].…”