Cellular and molecular mechanisms involved in the resolution of innate leukocyte inflammation

Abstract

Inflammation is a host response to infection or damage and is vital for clearing pathogens and host debris. When this resolution fails to occur, chronic inflammation ensues. Chronic inflammation is typically characterized as a low-grade, persistent inflammatory process that can last for months or even years. This differs from acute inflammation, which is typically a fast, robust response to a stimulus followed by resolution with return to homeostasis. Inflammation resolution occurs through a variety of cellular processes and signaling components that act as “brakes” to keep inflammation in check. In cases of chronic inflammation, these “brakes” are often dysfunctional. Due to its prevalent association with chronic diseases, there is growing interest in characterizing these negative regulators and their cellular effects in innate leukocytes. In this review, we aim to describe key cellular and molecular homeostatic regulators of innate leukocytes, with particular attention to the emerging regulatory processes of autophagy and lysosomal fusion during inflammation resolution.

Neutrophil Function Impairment Is a Host Susceptibility Factor to Bacterial Infection in Diabetes

“…Generally, this process is followed by macrophage autophagy [35,36]. Together, all these processes contribute to the resolution of neutrophil inflammation and tissue homeostasis [31].…”

“…Currently, it is known that resolution is an active and tightly controlled process, carried out by specialized pro-resolving mediators (SPM) such as resolvins, lipoxins, maresins, and protectins, which are produced locally from polyunsaturated fatty acids and act orchestrating the end of inflammation, but do not evoke unwanted immunosuppression [29,30]. For a correct resolution of inflammation, the neutrophil reverse migration, lymphatic drainage, exudation to the external environment, apoptosis of activated neutrophils followed by efferocytosis, and autophagic clearance of intracellular inflammatory signals are necessary [31,32].…”

Prolonged exposure to hypoxia induces an autophagy-like cell survival program in human neutrophils

“…The effects of hypoxia on these neutrophil functions could be beneficial for pathogen clearance, but could be detrimental for tissue injury and the resolution of inflammation . Interestingly, many of the neutrophil functional responses listed above have also been associated with increased autophagy, and our findings suggest that hypoxia‐induced autophagy may play a role in the observed modulation of neutrophil function in inflammation.…”

“…Changes in cell morphology and initiation of autophagosome formation were apparent within a few hours of hypoxia and persisted for at least 48 h, suggestive of an actively up‐regulated program of cell survival. Recent investigations have described the generation of autophagosomes in neutrophils as a process of lysosome and phagosome fusion, involving the activation of transcription factors and signaling proteins such as CREB and TFEB Tollip, IRAK‐M, and SIRT1 . There is accumulating evidence that activation of autophagy assists with neutrophil microbicidal activity and is an integral process in the regulation of neutrophil fate in inflammation .…”

Evaluation of Helicobacter pylori Infection, Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio in Dyspeptic Patients

“…In addition to that, B-cell response is produced both locally and systemically [18]. Activation of leukocytes occurs as a result of chronic inflammation; in other words, leukocytes have a role in chronic diseases, such as diabetes, hypertension, atherogenesis, thrombosis formation and other inflammatory disorders [19].…”