Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations.

Respiratory viruses are a major trigger of exacerbations in chronic obstructive pulmonary disease (COPD). Airway neutrophilia is a hallmark feature of stable and exacerbated COPD but roles played by neutrophil extracellular traps (NETS) in driving disease pathogenesis are unclear. Here, using human studies of experimentally-induced and naturally-occurring exacerbations we identify that rhinovirus infection induces airway NET formation which is amplified in COPD and correlates with magnitude of inflammation and clinical exacerbation severity.

CytoPipeline and CytoPipelineGUI: a Bioconductor R package suite for building and visualizing automated pre-processing pipelines for flow cytometry data.

Background: With the increase of the dimensionality in flow cytometry data over the past years, there is a growing need to replace or complement traditional manual analysis (i.e. iterative 2D gating) with automated data analysis pipelines.

IL-33-induced neutrophilic inflammation and NETosis underlie rhinovirus-triggered exacerbations of asthma.

Rhinovirus-induced neutrophil extracellular traps (NETs) contribute to acute asthma exacerbations; however, the molecular factors that trigger NETosis in this context remain ill-defined. Here, we sought to implicate a role for IL-33, an epithelial cell-derived alarmin rapidly released in response to infection. In mice with chronic experimental asthma (CEA), but not naïve controls, rhinovirus inoculation induced an early (1 day post infection; dpi) inflammatory response dominated by neutrophils, neutrophil-associated cytokines (IL-1α, IL-1β, CXCL1), and NETosis, followed by a later, type-2 inflammatory phase (3-7 dpi), characterised by eosinophils, elevated IL-4 levels, and goblet cell hyperplasia.

Effects of charge contrast and composition on microgel formation and interactions with bacteria-mimicking liposomes.

Microgels offer opportunities for improved delivery of antimicrobial peptides (AMP). To contribute to a foundation for rational design of such systems, we here study the effects of electrostatics on the generation of peptide-carrying microgels. For this, alginate microgels loaded with polymyxin B and cross-linked by Ca, were formed by electrostatic complexation using a hydrodynamic focusing three-dimensional (3D)-printed micromixer, varying pH and component concentrations.

Locally instructed CXCR4 neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps.

Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the chemokine receptor CXCR4 and to release neutrophil extracellular traps.

Sphagnum Species Modulate their Phenolic Profiles and Mycorrhizal Colonization of Surrounding Andromeda polifolia along Peatland Microhabitats.

Sphagnum mosses mediate long-term carbon accumulation in peatlands. Given their functional role as keystone species, it is important to consider their responses to ecological gradients and environmental changes through the production of phenolics. We compared the extent to which Sphagnum phenolic production was dependent on species, microhabitats and season, and how surrounding dwarf shrubs responded to Sphagnum phenolics.

Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations.

Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations.

Corrigendum: Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation.

This corrects the article DOI: 10.1038/nm.4332.

Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation.

Respiratory viral infections represent the most common cause of allergic asthma exacerbations. Amplification of the type-2 immune response is strongly implicated in asthma exacerbation, but how virus infection boosts type-2 responses is poorly understood. We report a significant correlation between the release of host double-stranded DNA (dsDNA) following rhinovirus infection and the exacerbation of type-2 allergic inflammation in humans.

Exposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages.

Living in a microbe-rich environment reduces the risk of developing asthma. Exposure of humans or mice to unmethylated CpG DNA (CpG) from bacteria reproduces these protective effects, suggesting a major contribution of CpG to microbe-induced asthma resistance. However, how CpG confers protection remains elusive.

Investigation of the Role of Protein Kinase D in Human Rhinovirus Replication.

Picornavirus replication is known to cause extensive remodeling of Golgi and endoplasmic reticulum membranes, and a number of the host proteins involved in the viral replication complex have been identified, including oxysterol binding protein (OSBP) and phosphatidylinositol 4-kinase III beta (PI4KB). Since both OSBP and PI4KB are substrates for protein kinase D (PKD) and PKD is known to be involved in the control of Golgi membrane vesicular and lipid transport, we hypothesized that PKD played a role in viral replication. We present multiple lines of evidence in support of this hypothesis.

Usefulness of Flow Cytometric Mepacrine Uptake/Release Combined with CD63 Assay in Diagnosis of Patients with Suspected Platelet Dense Granule Disorder.

Dense granule disorder is one of the most common platelet abnormalities, resulting from dense granule deficiency or secretion defect. This study was aimed to evaluate the clinical usefulness of the flow cytometric combination of mepacrine uptake/release assay and CD63 expression detection in the management of patients with suspected dense granule disorder. Over a period of 5 years, patients with abnormal platelet aggregation and/or reduced adenosine triphosphate (ATP) secretion suggestive of dense granule disorder were consecutively enrolled.

Role of interleukin 33 in respiratory allergy and asthma.

Since the discovery of interleukin 33 as the adopted ligand for the then orphan ST2 receptor, many studies have implicated this cytokine in the pathogenesis of respiratory allergy and asthma. Although some extracellular functions of interleukin 33 have been well defined, many aspects of the regulation and secretion of this cytokine need clarification. Interleukin 33 has been identified as a trigger of T-helper-type-2 cell differentiation, which by interacting with both the innate and the adaptive immune systems, can drive allergy and asthma pathogenesis.

Comparative evolution of oxygen, carbon dioxide, nitrogen, and sulfites during storage of a rosé wine bottled in PET and glass.

The management of dissolved and headspace gases during bottling and the choice of packaging are both key factors for the shelf life of wine. Two kinds of 75 cL polyethylene terephthalate (PET) bottles (with or without recycled PET) were compared to glass bottles filled with a rosé wine, closed with the same screwcaps and stored upright at 20 °C in light or in the dark. Analytical monitoring (aphrometric pressure, headspace volume, O2, N2, CO2, and SO2) was carried out for 372 days.

Resident CD11b(+)Ly6C(-) lung dendritic cells are responsible for allergic airway sensitization to house dust mite in mice.

Conventional dendritic cells (DCs) are considered to be the prime initiators of airway allergy. Yet, it remains unclear whether specific DC subsets are preferentially involved in allergic airway sensitization. Here, we systematically assessed the respective pro-allergic potential of individually sorted lung DC subsets isolated from house dust mite antigen (HDM)-treated donor mice, following transfer to naïve recipients.

Increased hypoxia-inducible factor 1α expression in lung cells of horses with recurrent airway obstruction.

Background: Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif) is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia.

Hemoglobin-based oxygen carriers do not alter platelet functions: study of three chemically modified hemoglobin solutions.

Objective: Chemically modified hemoglobins are being developed as potential oxygen-carrying blood substitutes (HBOCs). Clinical and preclinical data demonstrate the vasoactive properties of HBOCs by trapping of nitric oxide, which is also known to have platelet inhibitory activities properties. This study evaluated the effects of three structurally different HBOCs (Hb-Dex-BTC, alphaalpha-Hb, and o-raffinose-poly-Hb) on platelet functions in vitro to compare to those elicited by plasma substitutes, such as hydroxyethylstarch.