Neutrophils in Health and Disease: From Receptor Sensing to Inflammasome Activation

Abstract

Neutrophils—polymorphonuclear cells (PMNs) are the cells of the initial immune response and make up the majority of leukocytes in the peripheral blood. After activation, these cells modify their functional status to meet the needs at the site of action or according to the agent causing injury. They receive signals from their surroundings and “plan” the course of the response in both temporal and spatial contexts. PMNs dispose of intracellular signaling pathways that allow them to perform a wide range of functions associated with the development of inflammatory processes. In addition to these cells, some protein complexes, known as inflammasomes, also have a special role in the development and maintenance of inflammation. These complexes participate in the proteolytic activation of key pro-inflammatory cytokines, such as IL-1β and IL-18. In recent years, there has been significant progress in the understanding of the structure and molecular mechanisms behind the activation of inflammasomes and their participation in the pathogenesis of numerous diseases. The available reports focus primarily on macrophages and dendritic cells. According to the literature, the activation of inflammasomes in neutrophils and the associated death type—pyroptosis—is regulated in a different manner than in other cells. The present work is a review of the latest reports concerning the course of inflammasome activation and inflammatory cytokine secretion in response to pathogens in neutrophils, as well as the role of these mechanisms in the pathogenesis of selected diseases.

Bridging the Gap: Investigating the Link between Inflammasomes and Postoperative Cognitive Dysfunction

“…We further hypothesize that when local injury tissue releases inflammatory factors into circulation, it activates monocytes [108], neutrophils [108], NK cells [88], and platelets [109,110], which may then form inflammasomes within these cells, leading to more systemic inflammation and release of bone marrowderived monocytes (BMDMs). BMDMs and circulating inflammatory cytokines can access the brain via damaged BBB or areas lacking fully functional BBB, such as circumventricular organs [111], and penetrate brain tissue, leading to neuroinflammation.…”

Role of Mitochondria in the Chronification of Inflammation: Focus on Dysfunctional Mitophagy and Mitochondrial DNA Mutations

“…For example, mutations in genes encoding components of the NF-κB pathway or NLRP3 inflammasome can disrupt their normal function, leading to aberrant immune signaling. 62, 63 Besides, aging can unfavorably affect immune signaling pathways, leading to their dysregulation. Alterations in both NF-κB and NLRP3 inflammasome signaling have been implicated in age-related immune dysfunction and the development of low-grade inflammation.…”

Identifying Host and Bacterial Biomarkers to Predict Sepsis

“…Neutrophils are recruited to the site of injury/infection within minutes following chemotactic signals released at the site of infection (e.g., IL-8 and C5a) [134]. Neutrophils migrate through blood vessels via interactions between cell surface selectins and integrins and enter the site of infection where they act to further increase the local immune response through the release of inflammatory cytokines as well as direct killing of microbes through; phagocytosis, degranulation, and the release of reactive oxygen species (ROS [135].Neutrophils are usually short-lived cells which undergo constitutive apoptosis after the clearing of infection. Dying neutrophils are recognised by monocytes and macrophages, stimulating phagocytosis.…”