Neutrophil Extracellular Traps Go Viral

Neutrophils are the most numerous immune cells. Their importance as the first line of defense against bacterial and fungal pathogens is well described. In contrast, the role of neutrophils in controlling viral infections is less clear. Bacterial and fungal pathogens can stimulate neutrophils extracellular traps (NETs) in a process called NETosis. Although NETosis has previously been described as a special form of programmed cell death, there are forms of NET production that do not end with the demise of neutrophils. As an end result of NETosis, genomic DNA complexed with microbicidal proteins is expelled from neutrophils. These structures can kill pathogens or at least prevent their local spread within host tissue. On the other hand, disproportionate NET formation can cause local or systemic damage. Only recently, it was recognized that viruses can also induce NETosis. In this review, we discuss the mechanisms by which NETs are produced in the context of viral infection and how this may contribute to both antiviral immunity and immunopathology. Finally, we shed light on viral immune evasion mechanisms targeting NETs

Inflammatory responses to acute exercise during pulmonary rehabilitation in patients with COPD

Objective Pulmonary rehabilitation is a cornerstone treatment in the management of chronic obstructive pulmonary disease (COPD). Acute bouts of exercise can lead to short bursts of inflammation in healthy individuals. However, it is unclear how COPD patients respond to acute bouts of exercise. This study assessed inflammatory responses to exercise in COPD patients at the start (phase 1) and end (phase 2) of pulmonary rehabilitation. Methods Blood samples were collected before and after an acute exercise bout at the start (phase 1, n = 40) and end (phase 2, n = 27) of pulmonary rehabilitation. The primary outcome was change in fibrinogen concentrations. Secondary outcomes were changes in CRP concentrations, total/differential leukocyte counts, markers of neutrophil activation (CD11b, CD62L and CD66b), and neutrophil subsets (mature, suppressive, immature, progenitor). Results Acute exercise (phase 1) did not induce significant changes in fibrinogen (p = 0.242) or CRP (p = 0.476). Total leukocyte count [mean difference (MD), 0.5 ± 1.1 (109 L−1); p = 0.004], neutrophil count [MD, 0.4 ± 0.8 (109 L−1); p < 0.001], and immature neutrophils (MD, 0.6 ± 0.8%; p < 0.001) increased post-exercise. Neutrophil activation markers, CD11b (p = 0.470), CD66b (p = 0.334), and CD62L (p = 0.352) were not significantly altered post-exercise. In comparison to the start of pulmonary rehabilitation (phase 2), acute exercise at the end of pulmonary rehabilitation led to a greater fibrinogen response (MD, 84 mg/dL (95% CI − 14, 182); p = 0.045). Conclusion An acute bout of exercise does not appear to induce significant alterations in the concentrations of inflammatory mediators but can increase white blood cell subsets post-exercise. A greater fibrinogen response to acute exercise is seen at the end of pulmonary rehabilitation when compared to the start. Further research is required to understand the clinical context of these acute inflammatory responses to exercise

The Role of Eosinophils in Bullous Pemphigoid: A Developing Model of Eosinophil Pathogenicity in Mucocutaneous Disease

Bullous pemphigoid (BP) is an autoimmune blistering disease which carries a significant mortality and morbidity. While historically BP has been characterized as an IgG driven disease mediated by anti-BP180 and BP230 IgG autoantibodies, developments in recent years have further elucidated the role of eosinophils and IgE autoantibodies. In fact, eosinophil infiltration and eosinophilic spongiosis are prominent features in BP. Several observations support a pathogenic role of eosinophils in BP: IL-5, eotaxin, and eosinophil-colony stimulating factor are present in blister fluid; eosinophils line the dermo-epidermal junction (DEJ) in the presence of BP serum, metalloprotease-9 is released by eosinophils at the site of blisters; eosinophil degranulation proteins are found on the affected basement membrane zone as well as in serum corresponding with clinical disease; eosinophil extracellular DNA traps directed against the basement membrane zone are present, IL-5 activated eosinophils cause separation of the DEJ in the presence of BP serum; and eosinophils are the necessary cell required to drive anti-BP180 IgE mediated skin blistering. Still, it is likely that eosinophils contribute to the pathogenesis of BP in numerous other ways that have yet to be explored based on the known biology of eosinophils. We herein will review the role of eosinophils in BP and provide a framework for understanding eosinophil pathogenic mechanisms in mucocutaneous disease

Neutrophils in respiratory syncytial virus disease:Untangling the NET

Respiratory syncytial virus (RSV) is one of the most important causes of childhood pneumonia and bronchiolitis worldwide. The disease is accompanied by prominent neutrophilic inflammation of the airways. However, the precise role of these immune cells during the disease is largely unknown. The central focus of this thesis is the neutrophil, with the overall aim to increase our understanding of the role of this important innate immune cell in the pathogenesis of RSV lower respiratory tract disease (RSV-LRTD). In part I we go more into detail about two host-specific RSV animal models. We conclude that the bovine and human RSV model, together, mimic many aspects of human-RSV infection in young infants. In chapter 3 we explore another RSV animal model; the pneumonia virus of mice (PVM) model. We conclude that the PVM-model lacks activation of essential neutrophil effector functions needed to investigate the role of neutrophils during pneumovirus infections, this might be the explanation why we could not find any difference between neutrophil depleted and non-depleted mice in this RSV model. In chapter 4 we investigated if viral respiratory infections are accompanied by different neutrophil subsets and if these subsets could have either a suppressive phenotype or an activated phenotype. We could not find suppressive neutrophils in infants infected with virus alone, in contrast to infants with both viral and bacterial co-infection. In chapter 5 we summarise what is known about NET formation during (paediatric) respiratory diseases. In chapter 6 we investigated whether RSV was able to induce NET formation by human neutrophils in vitro, and if these NETs could trap viral particles and aid in the anti-viral response to RSV. Chapter 7 describes the effect of local dornase alfa treatment in bovine RSV infected calves. We found significant NET degradation during dornase alfa treatment compared to the control group, these results support the notion that treatment of NET-rich mucusplugs could alleviate airway obstruction. In chapter 8 we describe the build-up and functional characteristics of a panel of G-specific antibodies retrieved from humans. We found that these antibodies target specific epitopes in and around the conserved region of the G protein

The role of coagulation in ventilator-associated pneumonia

Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in the intensive care unit, and it is associated with prolonged hospitalization, increased health care costs, and high attributable mortality. Inflammatory changes in the pulmonary compartment as observed in acute lung injury are also often seen in VAP, and similar observations are now made regarding pulmonary coagulation changes. In the current review we will discuss the role of these coagulation changes in VAP (coagulopathy). We will discuss how mechanical ventilation affects both VAP and coagulopathy. As well as the role of anticoagulant therapies to reduce coagulopathy; from a theoretical perspective and from limited experimental research. And finally we will outline future research in this field

Italiaanse kaas uit Deurne : Buffel o Landa gaat buffelmelk verwerken tot mozzarella en die in Nederland

De veehouders in het bedrijf Buffel o Landa in Deurne gaan buffelmelk verwerken tot mozzarella en die in Nederland afzetten. Ook kijken de veehouders naar andere zuivelproducten die uit buffelmelk te maken zij

Italiaanse kaas uit Deurne : Buffel o Landa gaat buffelmelk verwerken tot mozzarella en die in Nederland

De veehouders in het bedrijf Buffel o Landa in Deurne gaan buffelmelk verwerken tot mozzarella en die in Nederland afzetten. Ook kijken de veehouders naar andere zuivelproducten die uit buffelmelk te maken zij

Neutrophil Extracellular Traps in Respiratory Disease: guided anti-microbial traps or toxic webs?

Neutrophil recruitment to the airways and lungs is a major hallmark of many respiratory diseases. One of the more recently discovered unique innate immune effector mechanisms of neutrophils is the formation of neutrophil extracellular traps (NETs), consisting of an extracellular network of DNA fibers studded with nuclear and granule proteins. Although in the respiratory system NETs contribute to capture and inactivation of bacteria, fungi and viruses, there is a delicate 'balance' between aid and damage to the host. Accumulating evidence now suggests that NETs can have direct cytotoxic effects to lung epithelial and endothelial cells and can contribute to airway obstruction. As such, NETs may play an important role in the pathogenesis of respiratory diseases. The purpose of this review is to give an up-to-date overview of the current status of NETs in respiratory diseases. We examine both experimental and clinical data concerning the role of NETs in host defence as well as immunopathology, with special attention paid to the literature relevant for the paediatric pulmonology community. Finally, we discuss future treatment strategies that may target the formation of NETs in the airways and lung

Human respiratory syncytial virus infection in the pre-clinical calf model

Human respiratory syncytial virus (hRSV) is the most important respiratory pathogen in young children worldwide. Experimental modelling of hRSV disease by bovine RSV (bRSV) infection in calves provides an important tool for developing new strategies for prevention and treatment. Depending on the scientific hypothesis under investigation, this cognate host-virus model might have the disadvantage of using a highly related but not genetically identical virus. In this study, we aim to describe viral kinetics and (clinical) disease characteristics in calves inoculated with hRSV. Our results show that hRSV infects the upper and, to a lesser extent, the lower respiratory tract of calves. Infection causes upper airway clinical disease symptoms and neutrophilic infiltration of the lower airways. We conclude that a hRSV model in calves may aid future research involving distinct scientific questions related to hRSV disease in children.</p