Neutrophils in acute inflammation: current concepts and translational implications

Abstract

Modulation of neutrophil recruitment and function is crucial for targeting inflammatory cells to sites of infection to combat invading pathogens while at the same time limiting host tissue injury or autoimmunity. The underlying mechanisms regulating recruitment of neutrophils, one of the most abundant inflammatory cells, have gained increasing interest over the years. The previously described classical recruitment cascade of leukocytes has been extended to include not only capturing, rolling, adhesion, crawling and transmigration but furthermore a reverse-transmigration step that is crucial for balancing immune defense and control of remote organ endothelial leakage. Current developments in the field emphasize the importance of cellular interplay, tissue-environmental cues, circadian rhythmicity, detection of neutrophil phenotypes, differential chemokine sensing, and contribution of distinct signaling components to receptor activation and integrin conformations. Use of therapeutics modulating neutrophil activation responses as well as mutations causing dysfunctional neutrophil receptors and impaired signaling cascades have been defined in translational animal models. Human correlates of such mutations result in increased susceptibility to infections or organ damage. This review focuses on current advances in the understanding of the regulation of neutrophil recruitment and functionality and translational implications of current discoveries in the field with a focus on acute inflammation and sepsis.

Neutrophil Extracellular Traps in Severe SARS-CoV-2 Infection: A Possible Impact of LPS and (1→3)-β-D-glucan in Blood from Gut Translocation

“…In general, neutrophils are promptly recruited into the site of infection, and neutrophilia is common at the very early phase of viral infections [ 48 , 49 ]. Indeed, neutrophils are the first-line immune cells in the acute phase of most infections (bacteria, viruses, and fungi) [ 50 , 51 ] and other non-infectious inflammatory conditions [ 52 ]. In most viral infections, neutrophil numbers peak during the early phase of infections, follow by neutrophil reduction and lymphocyte elevation (lymphocytosis).…”

Mesenchymal stem cell homing to improve therapeutic efficacy in liver disease

“…Upon activation of endothelial cells, the interaction between upregulated P-selectin, L-selectin, E-selectin, P-selectin glycoprotein ligand 1, E-selectin ligand or s-Lex expressed on leukocytes mediates the binding and rolling of leukocytes, which is a prerequisite for cell migration [ 72 ]. Interestingly, Rüster et al found that MSCs bind to endothelial cells in a P-selectin-dependent manner [ 73 ].…”

Immune Cell Plasticity in Inflammation: Insights into Description and Regulation of Immune Cell Phenotypes

“…Sepsis evokes the extravasation of leukocytes and consumption of platelets [ 39 , 40 ]. Such events demand replenishing and mobilization of cellular pools to outweigh cellular deficiencies within the circulation [ 40 ].…”

“…Sepsis evokes the extravasation of leukocytes and consumption of platelets [ 39 , 40 ]. Such events demand replenishing and mobilization of cellular pools to outweigh cellular deficiencies within the circulation [ 40 ]. HSCs express Toll-like receptors, which trigger myeloid differentiation and aid in replenishment of innate immune cells during infection [ 41 ].…”

“…Of note, ageing is also associated with disturbances in circadian rhythms, leading to imbalances in immune cell responses [ 81 ], and likewise, disturbed circadian rhythmicity due to genetic targeting of BMAL1 leads to premature ageing [ 82 ]. As for the cell-intrinsic maturation and ageing, aged neutrophils feature high CXCR4 expression, which mediates their clearance within the bone marrow [ 40 , 49 ]. In contrast to the notion of an aged cell as an exhausted “retired” cell, these are actually well-educated, “trained” and easily activatable cells, aiding in the immediate immune defense response [ 83 , 84 ].…”