The bacterial serine protease inhibitor ecotin inhibits neutrophil elastase enzymatic activity in cystic fibrosis sputa.

Cystic Fibrosis (CF) airway disease is characterized by impaired mucociliary clearance, chronic, polymicrobial infections and robust, neutrophil-dominated inflammation. Pulmonary disease is the leading cause of morbidity and mortality in people with CF and is due to progressive airflow obstruction and ultimately respiratory failure. One of the earliest abnormalities in CF airway disease is the recruitment of neutrophils to the lungs.

Flagellum-deficient is more virulent than non-motile but flagellated mutants in a cystic fibrosis mouse model.

Loss of the flagellum marks the pathoadaptation of to the cystic fibrosis (CF) airway environment during lung disease. Losing the flagellum is advantageous to the bacterium as the flagellum can be recognized by immune cells. The primary purpose of the flagellum is, however, to provide motility to the bacterium.

The therapeutic potential of thiocyanate and hypothiocyanous acid against pulmonary infections.

Hypothiocyanous acid (HOSCN) is an endogenous oxidant produced by peroxidase oxidation of thiocyanate (SCN), an ubiquitous sulfur-containing pseudohalide synthesized from cyanide. HOSCN serves as a potent microbicidal agent against pathogenic bacteria, viruses, and fungi, functioning through thiol-targeting mechanisms, independent of currently approved antimicrobials. Additionally, SCN reacts with hypochlorous acid (HOCl), a highly reactive oxidant produced by myeloperoxidase (MPO) at sites of inflammation, also producing HOSCN.

Bone marrow stromal cell-derived hepcidin has antimicrobial and immunomodulatory activities.

Bone marrow stromal cells (BMSCs) have immunomodulatory activities in numerous species and have been used in clinical trials. BMSCs also make antibacterial agents. Since hepcidin is known to have antimicrobial effects in fish, we wondered if it might also be used as an antimicrobial agent by mammalian BMSCs.

Variant-dependent oxidative and cytokine responses of human neutrophils to SARS-CoV-2 spike protein and anti-spike IgG1 antibodies.

Introduction: Severe forms of COVID-19, the disease caused by SARS-CoV-2, are characterized by acute respiratory distress syndrome, robust lung inflammation and death in some patients. Strong evidence has been accumulating that polymorphonuclear neutrophilic granulocytes (PMN) play an important role in the pathophysiology of severe COVID-19. SARS-CoV-2 directly induces PMN activation, mainly the release of neutrophil extracellular traps (NETs).

Cystic fibrosis autoantibody signatures associate with lung infection or cystic fibrosis-related diabetes.

Introduction: While cystic fibrosis (CF) lung disease is characterized by persistent inflammation and infections and chronic inflammatory diseases are often accompanied by autoimmunity, autoimmune reactivity in CF has not been studied in depth.

Methods: In this work we undertook an unbiased approach to explore the systemic autoantibody repertoire in CF using autoantibody microarrays.

Results And Discussion: Our results show higher levels of several new autoantibodies in the blood of people with CF (PwCF) compared to control subjects.

Sputum from People with Cystic Fibrosis Reduces the Killing of Methicillin-Resistant by Neutrophils and Diminishes Phagosomal Production of Reactive Oxygen Species.

Cystic fibrosis (CF) airway disease is characterized by chronic polymicrobial infections and an infiltration of neutrophils (PMNs). has been the most prevalent respiratory pathogen in CF. In particular, methicillin-resistant (MRSA) represents a huge clinical burden in CF due to its association with lung disease and increased resistance to antibiotics.

Short chain fatty acids reduce the respiratory burst of human neutrophils in response to cystic fibrosis isolates of Staphylococcus aureus.

Short chain fatty acids (SCFA) are produced by anaerobic bacteria. The most common SCFAs are acetate, propionate and butyrate. SCFAs have been implicated in several inflammatory diseases including cystic fibrosis (CF) where they are present in the airways at millimolar concentrations.

Dual oxidase 1 is dispensable during infection in mice.

Introduction: (Mtb) is the primary cause of human tuberculosis (TB) and is currently the second most common cause of death due to a singleinfectious agent. The first line of defense against airborne pathogens, including Mtb, is the respiratory epithelium. One of the innate defenses used by respiratory epithelial cells to prevent microbial infection is an oxidative antimicrobial system consisting of the proteins, lactoperoxidase (LPO) and Dual oxidase 1 (Duox1), the thiocyanate anion (SCN-) and hydrogen peroxide (H2O2), which together lead to the generation of antimicrobial hypothiocyanite (OSCN-) in the airway lumen.

The Hypothiocyanite and Amantadine Combination Treatment Prevents Lethal Influenza A Virus Infection in Mice.

The influenza virus has a large clinical burden and is associated with significant mortality and morbidity. The development of effective drugs for the treatment or prevention of influenza is important in order to reduce its impact. Adamantanes and neuraminidase inhibitors are two classes of anti-influenza drugs in which resistance has developed; thus, there is an urgent need to explore new therapeutic options.

Serum anti-PAD4 autoantibodies are present in cystic fibrosis children and increase with age and lung disease severity.

Cystic fibrosis (CF) lung disease begins early in childhood and is characterized by neutrophilic inflammation of the airways. Neutrophil extracellular traps (NETs) represent one mechanism by which neutrophils contribute to lung damage. The enzyme peptidylarginine deiminase 4 (PAD4) is required for NET formation.

RGS10 Reduces Lethal Influenza Infection and Associated Lung Inflammation in Mice.

Seasonal influenza epidemics represent a significant global health threat. The exacerbated immune response triggered by respiratory influenza virus infection causes severe pulmonary damage and contributes to substantial morbidity and mortality. Regulator of G-protein signaling 10 (RGS10) belongs to the RGS protein family that act as GTPase activating proteins for heterotrimeric G proteins to terminate signaling pathways downstream of G protein-coupled receptors.

Microbicidal Activity of Hypothiocyanite against Pneumococcus.

Infections caused by (pneumococcus, ) manifest in several forms such as pneumonia, meningitis, sinusitis or otitis media and are associated with severe morbidity and mortality worldwide. While current vaccines and antibiotics are available to treat infections, the rise of antibiotic resistance and limitations of the vaccines to only certain serotypes urge the development of novel treatments against . Hypothiocyanite (OSCN-) is a natural antimicrobial product produced by the body's own innate immune system to fight a variety of pathogens.

Myeloperoxidase and Other Markers of Neutrophil Activation Associate With Malaria and Malaria/HIV Coinfection in the Human Placenta.

Introduction: Placental malaria (PM) is characterized by accumulation of inflammatory leukocytes in the placenta, leading to poor pregnancy outcomes. Understanding of the underlying mechanisms remains incomplete. Neutrophils respond to malaria parasites by phagocytosis, generation of oxidants, and externalization of Neutrophil Extracellular Traps (NETs).

Granulocytic Myeloid-Derived Suppressor Cells in Cystic Fibrosis.

Cystic Fibrosis (CF) is a genetic disease that causes chronic and severe lung inflammation and infection associated with high rates of mortality. In CF, disrupted ion exchange in the epithelium results in excessive mucus production and reduced mucociliary clearance, leading to immune system exacerbation and chronic infections with pathogens such as and . Constant immune stimulation leads to altered immune responses including T cell impairment and neutrophil dysfunction.

PI3K/ NF-κB-dependent TNF-α and HDAC activities facilitate LPS-induced RGS10 suppression in pulmonary macrophages.

Regulator of G-protein signaling 10 (RGS10) is a member of the superfamily of RGS proteins that canonically act as GTPase activating proteins (GAPs). RGS proteins accelerate GTP hydrolysis on the G-protein α subunits and result in termination of signaling pathways downstream of G protein-coupled receptors. Beyond its GAP function, RGS10 has emerged as an anti-inflammatory protein by inhibiting LPS-mediated NF-κB activation and expression of inflammatory cytokines, in particular TNF-α.

Modeling Immune Evasion and Vaccine Limitations by Targeted Nasopharyngeal Bordetella pertussis Inoculation in Mice.

Conventional pertussis animal models deliver hundreds of thousands of Bordetella pertussis bacteria deep into the lungs, rapidly inducing severe pneumonic pathology and a robust immune response. However, human infections usually begin with colonization and growth in the upper respiratory tract. We inoculated only the nasopharynx of mice to explore the course of infection in a more natural exposure model.

Cystic Fibrosis Sputum Impairs the Ability of Neutrophils to Kill .

Cystic fibrosis (CF) airway disease is characterized by chronic microbial infections and infiltration of inflammatory polymorphonuclear (PMN) granulocytes. is a major lung pathogen in CF that persists despite the presence of PMNs and has been associated with CF lung function decline. While PMNs represent the main mechanism of the immune system to kill , it remains largely unknown why PMNs fail to eliminate in CF.

Dual oxidase 1 promotes antiviral innate immunity.

Dual oxidase 1 (DUOX1) is an NADPH oxidase that is highly expre-ssed in respiratory epithelial cells and produces HO in the airway lumen. While a line of prior in vitro observations suggested that DUOX1 works in partnership with an airway peroxidase, lactoperoxidase (LPO), to produce antimicrobial hypothiocyanite (OSCN) in the airways, the in vivo role of DUOX1 in mammalian organisms has remained unproven to date. Here, we show that Duox1 promotes antiviral innate immunity in vivo.

DUOX1 in mammalian disease pathophysiology.

Dual oxidase 1 (DUOX1) is a member of the protein family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. DUOX1 has several normal physiological, immunological, and biochemical functions in different parts of the body. Dysregulated oxidative metabolism interferes with various disease pathologies and numerous therapeutic options are based on targeting cellular redox pathways.

"NETs and EETs, a Whole Web of Mess".

Neutrophils and eosinophils are granulocytes that have very distinct functions. Neutrophils are first responders to external threats, and they use different mechanisms to control pathogens. Phagocytosis, reactive oxygen species, and neutrophil extracellular traps (NETs) are some of the mechanisms that neutrophils utilize to fight pathogens.