Therapeutic Application of an Extract of Ameliorates the Development of Allergic Airway Disease.

Epidemiological and experimental studies have shown that exposure to the gastric bacterium , especially in early life, prevents the development of asthma. Recent mouse studies have shown that this protective effect does not require live bacteria and that treatment with an extract of in neonates prevents the development of airway inflammation and goblet cell metaplasia. In the current study, the effect of administration of an extract of was assessed in a therapeutic study design with application of the extract just prior to allergen challenge.

Spleen-derived IFN-γ induces generation of PD-L1-suppressive neutrophils during endotoxemia.

The immune inhibitory checkpoint molecule programmed death ligand (PD-L)-1 is increasingly recognized as an important player in the immune suppression observed in patients with sepsis, but its role has mainly been studied in monocytes. In an earlier study, we demonstrated that experimental human endotoxemia results in mobilization of a subset of PD-L1-expressing neutrophils displaying an IFN-γ-induced transcriptome profile. Herein, we identify the source of IFN-γ production during murine endotoxemia and its role in the generation of PD-L1-suppressive neutrophils.

Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development.

Background: COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD), and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC) possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases.

The effect of tiotropium in combination with olodaterol on house dust mite-induced allergic airway disease.

One of the major goals of asthma therapy is to maintain asthma control and prevent acute exacerbations. Long-acting bronchodilators are regularly used for the treatment of asthma patients and in clinical studies the anti-cholinergic tiotropium has recently been shown to reduce exacerbations in patients with asthma. So far it is unclear how tiotropium exerts this effect.

A short-term extremely low frequency electromagnetic field exposure increases circulating leukocyte numbers and affects HPA-axis signaling in mice.

There is still uncertainty whether extremely low frequency electromagnetic fields (ELF-EMF) can induce health effects like immunomodulation. Despite evidence obtained in vitro, an unambiguous association has not yet been established in vivo. Here, mice were exposed to ELF-EMF for 1, 4, and 24 h/day in a short-term (1 week) and long-term (15 weeks) set-up to investigate whole body effects on the level of stress regulation and immune response.

Microorganism-induced suppression of allergic airway disease: novel therapies on the horizon?

Allergic airway disease is a major global health burden, and novel treatment options are urgently needed. Numerous epidemiological and experimental studies suggest that certain helminths and bacteria protect against respiratory allergies. These microorganisms are strong regulators of the immune system, and various potential regulatory mechanisms by which they protect against allergic airway inflammation have been proposed.

IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1.

During systemic inflammation different neutrophil subsets are mobilized to the peripheral blood. These neutrophil subsets can be distinguished from normal circulating neutrophils (CD16(bright)/CD62L(bright)), based on either an immature CD16(dim)/CD62L(bright) or a CD16(bright)/CD62L(dim) phenotype. Interestingly, the latter neutrophil subset is known to suppress lymphocyte proliferation ex vivo, but how neutrophils become suppressive is unknown.

Bacterial lipopolysaccharide inhibits influenza virus infection of human macrophages and the consequent induction of CD8+ T cell immunity.

It is well established that infection with influenza A virus (IAV) facilitates secondary bacterial disease. However, there is a growing body of evidence that the microbial context in which IAV infection occurs can affect both innate and adaptive responses to the virus. To date, these studies have been restricted to murine models of disease and the relevance of these findings in primary human cells remains to be elucidated.

Modulation of granulocyte kinetics by GM-CSF/IFN-γ in a human LPS rechallenge model.

Inflammation in response to infection or trauma can lead to CARS, which is characterized by leukocyte dysfunction. In this study, we used a human model system for CARS to study the effect of GM-CSF and IFN-γ treatment on this immunoparalyzed state. Healthy human volunteers were treated with GM-CSF (4 μg/kg), IFN-γ (100 μg), or placebo in between two challenges with Escherichia coli LPS/endotoxin (2 ng/kg).

Transcriptome kinetics of circulating neutrophils during human experimental endotoxemia.

Polymorphonuclear cells (neutrophils) play an important role in the systemic inflammatory response syndrome and the development of sepsis. These cells are essential for the defense against microorganisms, but may also cause tissue damage. Therefore, neutrophil numbers and activity are considered to be tightly regulated.

Low-frequency electromagnetic fields do not alter responses of inflammatory genes and proteins in human monocytes and immune cell lines.

The effects of low frequency electromagnetic fields (LF EMF) on human health are the subject of on-going research and serious public concern. These fields potentially elicit small effects that have been proposed to have consequences, either positive or negative, for biological systems. To reveal potentially weak but biologically relevant effects, we chose to extensively examine exposure of immune cells to two different signals, namely a complex multiple waveform field, and a 50 Hz sine wave.

Differential ex vivo and in vivo endotoxin tolerance kinetics following human endotoxemia.

Objectives: Endotoxin (lipopolysaccharide) tolerance is characterized by a transient refractory state to a subsequent lipopolysaccharide challenge. Following human endotoxemia, ex vivo tolerance of circulating leukocytes to lipopolysaccharide resolves within 24 hrs. However, the duration of in vivo tolerance, assumed to be primarily mediated by tissue-resident macrophages, is unknown.

Extremely low frequency electromagnetic field exposure does not modulate toll-like receptor signaling in human peripheral blood mononuclear cells.

The effects of extremely low frequency electromagnetic fields (ELF-EMF) on human health remain unclear. It has been reported that ELF-EMF may modulate the innate immune response to microorganisms in animal models and mammalian cell-lines. With the recently gained insight in innate immune signaling and the discovery of pattern recognition, we aim to study whether ELF-EMF modulates innate inflammatory signaling pathways.

Surface-exposed histone-like protein a modulates adherence of Streptococcus gallolyticus to colon adenocarcinoma cells.

Streptococcus gallolyticus (formerly known as Streptococcus bovis biotype I) is a low-grade opportunistic pathogen which is considered to be associated with colon cancer. It is thought that colon polyps or tumors are the main portal of entry for this bacterium and that heparan sulfate proteoglycans (HSPGs) at the colon tumor cell surface are involved in bacterial adherence during the first stages of infection. In this study, we have shown that the histone-like protein A (HlpA) of S.