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Immunological Reviews Jul 2009Beta-glucans are recognized by the innate immune system. This recognition plays important roles in host defense and presents specific opportunities for clinical... (Review)
Review
Beta-glucans are recognized by the innate immune system. This recognition plays important roles in host defense and presents specific opportunities for clinical modulation of the host immune response. Neutrophils, macrophages, and dendritic cells among others express several receptors capable of recognizing beta-glucan in its various forms. This review explores what is currently known about beta-glucan recognition and how this recognition stimulates immune responses. Special emphasis is placed on Dectin-1, as we know the most about how this key beta-glucan receptor translates recognition into intracellular signaling, stimulates cellular responses, and participates in orchestrating the adaptive immune response.
Topics: Animals; Fungi; Humans; Immunity, Active; Immunity, Innate; Lectins, C-Type; Membrane Proteins; Nerve Tissue Proteins; Phagocytosis; Receptors, Immunologic; Respiratory Burst; Signal Transduction; Transcriptional Activation; beta-Glucans
PubMed: 19594628
DOI: 10.1111/j.1600-065X.2009.00793.x -
Frontiers in Immunology 2019Neutrophils are the most abundant innate immune cells. The pathogenic roles of neutrophils are related to chronic inflammation and autoimmune diseases. Psoriasis is a... (Review)
Review
Neutrophils are the most abundant innate immune cells. The pathogenic roles of neutrophils are related to chronic inflammation and autoimmune diseases. Psoriasis is a chronic systemic inflammatory disease affecting ~2-3% of the world population. The abundant presence of neutrophils in the psoriatic skin lesions serves as a typical histopathologic hallmark of psoriasis. Recent reports indicated that oxidative stress, granular components, and neutrophil extracellular traps from psoriatic neutrophils are related to the initial and maintenance phases of psoriasis. This review provides an overview on the recent (up to 2019) advances in understanding the role of neutrophils in the pathophysiology of psoriasis, including the effects of respiratory burst, degranulation, and neutrophil extracellular trap formation on psoriatic immunity and the clinical relationships.
Topics: Extracellular Traps; Humans; Immunity, Innate; Neutrophils; Psoriasis; Respiratory Burst
PubMed: 31649677
DOI: 10.3389/fimmu.2019.02376 -
Cell Reports Feb 2023Neutrophils are critical in the host defense against Staphylococcus aureus, a major human pathogen. However, even in the setting of a robust neutrophil response,...
Neutrophils are critical in the host defense against Staphylococcus aureus, a major human pathogen. However, even in the setting of a robust neutrophil response, S. aureus can evade immune clearance. Here, we demonstrate that S. aureus impairs neutrophil function by triggering the production of the anti-inflammatory metabolite itaconate. The enzyme that synthesizes itaconate, Irg1, is selectively expressed in neutrophils during S. aureus pneumonia. Itaconate inhibits neutrophil glycolysis and oxidative burst, which impairs survival and bacterial killing. In a murine pneumonia model, neutrophil Irg1 expression protects the lung from excessive inflammation but compromises bacterial clearance. S. aureus is thus able to evade the innate immune response by targeting neutrophil metabolism and inducing the production of the anti-inflammatory metabolite itaconate.
Topics: Humans; Animals; Mice; Staphylococcus aureus; Neutrophils; Respiratory Burst; Staphylococcal Infections
PubMed: 36724077
DOI: 10.1016/j.celrep.2023.112064 -
International Journal of Environmental... Feb 2021Systemic inflammatory response syndrome (SIRS) is defined as the systemic host response to infection or a non-infectious factor. The purpose of this study was to...
Systemic inflammatory response syndrome (SIRS) is defined as the systemic host response to infection or a non-infectious factor. The purpose of this study was to evaluate the involvement of reactive oxygen species (ROS) in severe inflammation and to assess the discrimination strength of the neutrophil BURSTTEST assay regarding its etiology in three groups of patients (sepsis, burns, and bone fractures) who met the SIRS criteria. The neutrophil activation (respiratory burst of granulocytes as well as p55 and p75 tumor necrosis factor (TNF-α) receptor expression) was evaluated twice using flow cytometry, and the results were compared with healthy controls and among SIRS subjects. A decreased oxygen metabolism in neutrophils after stimulation and increased TNF-α receptor expression were found in septic and burned patients on admission, while ROS production augmented and TNF-α receptor expression diminished with the applied therapy. The significant differences in neutrophil respiratory burst intensity among septic and burned patients and those with sepsis and bone fractures were found (however, there were not any such differences between patients with thermal and mechanical injuries). This study indicates that the neutrophil BURSTTEST evaluation might be a clinically reliable marker for differentiating the SIRS etiology.
Topics: Child; Humans; Inflammation; Neutrophils; Respiratory Burst; Sepsis; Tumor Necrosis Factor-alpha
PubMed: 33672270
DOI: 10.3390/ijerph18042187 -
Free Radical Biology & Medicine Aug 2021The small GTPase Arf6 regulates many cellular processes, including cytoskeletal remodeling, receptor endocytosis, and pathogen phagocytosis. Arf6 silencing in neutrophil... (Review)
Review
The small GTPase Arf6 regulates many cellular processes, including cytoskeletal remodeling, receptor endocytosis, and pathogen phagocytosis. Arf6 silencing in neutrophil (PMN)-like cells is well-known to inhibit chemotactic peptide-mediated activation of phospholipase D, the oxidative burst, and β2 integrin-dependent adhesion. In conditional knockout (cKO) mice, the migration to inflammatory sites of Arf6-deficient PMNs was diminished and associated with reduced cell surface expression of β2 integrins. In this study we assessed the impact of Arf6 depletion on the functions and gene expression profile of PMNs isolated from the mouse air pouch. Numerous genes involved in response to oxygen levels, erythrocyte and myeloid differentiation, macrophage chemotaxis, response to chemicals, apoptosis, RNA destabilization, endosome organization, and vesicle transport were differentially expressed in PMNs cKO for Arf6. Lpar6 and Lacc-1 were the most up-regulated and down-regulated genes, respectively. The deletion of Arf6 also decreased Lacc-1 protein level in PMNs, and silencing of Arf6 in THP-1 monocytic cells delayed LPS-mediated Lacc-1 expression. We report that fMLP or zymosan-induced glycolysis and oxygen consumption rate were both decreased in air pouch PMNs but not in bone marrow PMNs of Arf6 cKO mice. Reduced oxygen consumption correlated with a decrease in superoxide and ROS production. Deletion of Arf6 in PMNs also reduced phagocytosis and interfered with apoptosis. The data suggest that Arf6 regulates energy metabolism, which may contribute to impaired phagocytosis, ROS production, and apoptosis in PMN-Arf6 cKO. This study provides new information on the functions and the inflammatory pathways influenced by Arf6 in PMNs.
Topics: Animals; Energy Metabolism; Mice; Neutrophils; Phagocytosis; Respiratory Burst; Superoxides
PubMed: 34245858
DOI: 10.1016/j.freeradbiomed.2021.07.001 -
Redox Biology Nov 2021The respiratory burst of phagocytes is essential for human survival. Innate immune defence against pathogens relies strongly on reactive oxygen species (ROS) production...
The respiratory burst of phagocytes is essential for human survival. Innate immune defence against pathogens relies strongly on reactive oxygen species (ROS) production by the NADPH oxidase (NOX2). ROS kill pathogens while the translocation of electrons across the plasma membrane via NOX2 depolarizes the cell. Simultaneously, protons are released into the cytosol. Here, we compare freshly isolated human polymorphonuclear leukocytes (PMN) to the granulocytes-like cell line PLB 985. We are recording ROS production while inhibiting the charge compensating and pH regulating voltage-gated proton channel (H1). The data suggests that human PMN and the PLB 985 generate ROS via a general mechanism, consistent of NOX2 and H1. Additionally, we advanced a mathematical model based on the biophysical properties of NOX2 and H1. Our results strongly suggest the essential interconnection of H1 and NOX2 during the respiratory burst of phagocytes. Zinc chelation during the time course of the experiments postulates that zinc leads to an irreversible termination of the respiratory burst over time. Flow cytometry shows cell death triggered by high zinc concentrations and PMA. Our data might help to elucidate the complex interaction of proteins during the respiratory burst and contribute to decipher its termination.
Topics: Humans; Ion Channels; NADPH Oxidases; Neutrophils; Reactive Oxygen Species; Respiratory Burst; Zinc
PubMed: 34562872
DOI: 10.1016/j.redox.2021.102133 -
Journal of Infection in Developing... Oct 2018Hormonal and metabolic changes, as well as energy imbalance, can affect health, production and reproductive performance of dairy cows. In the present study, we evaluated...
INTRODUCTION
Hormonal and metabolic changes, as well as energy imbalance, can affect health, production and reproductive performance of dairy cows. In the present study, we evaluated phagocytosis and respiratory burst neutrophil activity during the transition period and early lactation and compared it with biochemical and hematological parameters in dairy cows.
METHODOLOGY
Simmental cows (n = 21) were enrolled in the study. Whole blood samples were collected weekly from 3 weeks pre- calving until 6 weeks post calving. Basic metabolic and blood parameters were assessed by routine laboratory analyses, while neutrophil functions were analyzed by commercial test kits.
RESULTS
Optimal neutrophil response was observed pre and post calving. The highest value was recorded in the 6th week after calving (89.54 ± 7.61%) and being significantly higher (p < 0.01) as compared to values recorded at two and one week before and one week after calving. The percentage of activated neutrophils was high during the entire study period: from 70.80 ± 5.22% at the beginning of the study to 89.54 ± 7.61% at the end of the study. During the study period, production of Reactive Oxidative Species by neutrophils was positively correlated with β-hydroxybutyrat and non-esterified fatty acids values (0.454** and 0.423**, respectively) and calcium levels (0.164* and 0.212**, respectively).
CONCLUSIONS
The most prominent changes in all parameters had no influence on phagocytic and respiratory burst activity of neutrophils. Neutrophil function is preserved at the optimal level during the transition period and early lactation in Simmental cows.
Topics: Animals; Calcium; Cattle; Female; Lactation; Magnesium; Milk; Neutrophils; Phagocytosis; Phosphorus; Pregnancy; Pregnancy, Animal; Respiratory Burst
PubMed: 32004159
DOI: 10.3855/jidc.10767 -
Frontiers in Immunology 2022Neutrophils play a significant role in determining disease severity following SARS-CoV-2 infection. Gene and protein expression defines several neutrophil clusters in...
Neutrophils play a significant role in determining disease severity following SARS-CoV-2 infection. Gene and protein expression defines several neutrophil clusters in COVID-19, including the emergence of low density neutrophils (LDN) that are associated with severe disease. The functional capabilities of these neutrophil clusters and correlation with gene and protein expression are unknown. To define host defense and immunosuppressive functions of normal density neutrophils (NDN) and LDN from COVID-19 patients, we recruited 64 patients with severe COVID-19 and 26 healthy donors (HD). Phagocytosis, respiratory burst activity, degranulation, neutrophil extracellular trap (NET) formation, and T-cell suppression in those neutrophil subsets were measured. NDN from severe/critical COVID-19 patients showed evidence of priming with enhanced phagocytosis, respiratory burst activity, and degranulation of secretory vesicles and gelatinase and specific granules, while NET formation was similar to HD NDN. COVID LDN response was impaired except for enhanced NET formation. A subset of COVID LDN with intermediate CD16 expression (CD16 LDN) promoted T cell proliferation to a level similar to HD NDN, while COVID NDN and the CD16 LDN failed to stimulate T-cell activation. All 3 COVID-19 neutrophil populations suppressed stimulation of IFN-γ production, compared to HD NDN. We conclude that NDN and LDN from COVID-19 patients possess complementary functional capabilities that may act cooperatively to determine disease severity. We predict that global neutrophil responses that induce COVID-19 ARDS will vary depending on the proportion of neutrophil subsets.
Topics: COVID-19; Extracellular Traps; Humans; Neutrophils; Respiratory Burst; SARS-CoV-2
PubMed: 35711435
DOI: 10.3389/fimmu.2022.879686 -
The Journal of Trauma and Acute Care... Feb 2022Trauma increases susceptibility to secondary bacterial infections. The events suppressing antimicrobial immunity are unclear. Polymorphonuclear neutrophils (PMNs)...
BACKGROUND
Trauma increases susceptibility to secondary bacterial infections. The events suppressing antimicrobial immunity are unclear. Polymorphonuclear neutrophils (PMNs) migrate toward bacteria using chemotaxis, trap them in extracellular neutrophil extracellular traps, and kill them using respiratory burst (RB). We hypothesized that plasma and wound fluids from trauma patients alter PMN function.
METHODS
Volunteer PMNs were incubated in plasma or wound fluids from trauma patients (days 0 and 1, days 2 and 3), and their functions were compared with PMNs incubated in volunteer plasma. Chemotaxis was assessed in transwells. Luminometry assessed total and intracellular RB responses to receptor-dependent and independent stimulants. Neutrophil extracellular trap formation was assessed using elastase assays. The role of tissue necrosis in creating functionally suppressive systemic PMN environments was assessed using a novel pig model where PMNs were incubated in uninjured pig plasma or plasma from pigs undergoing intraperitoneal instillation of liver slurry.
RESULTS
Both plasma and wound fluids from trauma patients markedly suppress total PMN RB. Intracellular RB is unchanged, implicating suppression of extracellular RB. Wound fluids are more suppressive than plasma. Biofluids suppressed RB maximally early after injury and their effects decayed with time. Chemotaxis and neutrophil extracellular trap formation were suppressed by biofluids similarly. Lastly, plasma from pigs undergoing abdominal liver slurry instillation suppressed PMN RB, paralleling suppression by human trauma biofluids.
CONCLUSION
Trauma plasma and wound fluids suppress RB and other key PMNs antimicrobial functions. Circulating suppressive signals can be derived from injured or necrotic tissue at wound sites, suggesting a key mechanism by which tissue injuries can put the host at risk for infection.
Topics: Animals; Chemotaxis; Exudates and Transudates; Humans; Neutrophils; Plasma Volume; Respiratory Burst; Swine; Wounds and Injuries
PubMed: 34789698
DOI: 10.1097/TA.0000000000003461 -
Journal of Leukocyte Biology Sep 2022Inflammatory agents, microbial products, or stromal factors pre-activate or prime neutrophils to respond to activating stimuli in a rapid and aggressive manner. Primed...
Inflammatory agents, microbial products, or stromal factors pre-activate or prime neutrophils to respond to activating stimuli in a rapid and aggressive manner. Primed neutrophils exhibit enhanced chemotaxis, phagocytosis, and respiratory burst when stimulated by secondary activating stimuli. We previously reported that Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) mediates neutrophil effector functions such as increased superoxide generation, transepithelial migration, and chemotaxis. However, it is unclear whether TREM-1 is required for the process of priming itself or for primed responses to subsequent stimulation. To investigate this, we utilized in vitro and in vivo differentiated neutrophils that were primed with TNF-α and then stimulated with the particulate agonist, opsonized zymosan (OpZ). Bone marrow progenitors isolated from WT and Trem-1 mice were transduced with estrogen regulated Homeobox8 (ER-Hoxb8) fusion transcription factor and differentiated in vitro into neutrophils following estrogen depletion. The resulting neutrophils expressed high levels of TREM-1 and resembled mature in vivo differentiated neutrophils. The effects of priming on phagocytosis and oxidative burst were determined. Phagocytosis did not require TREM-1 and was not altered by priming. In contrast, priming significantly enhanced OpZ-induced oxygen consumption and superoxide production in WT but not Trem-1 neutrophils indicating that TREM-1 is required for primed oxidative burst. TREM-1-dependent effects were not mediated during the process of priming itself as priming enhanced degranulation, ICAM-1 shedding, and IL-1ß release to the same extent in WT and Trem-1 neutrophils. Thus, TREM-1 plays a critical role in primed phagocytic respiratory burst and mediates its effects following priming.
Topics: Animals; Mice; Neutrophils; Respiratory Burst; Superoxides; Triggering Receptor Expressed on Myeloid Cells-1; Zymosan
PubMed: 35075692
DOI: 10.1002/JLB.3A0421-212R