The intestinal commensal fungus Wallemia mellicola enhances asthma in mice through Dectin-2.

Overgrowth of the fungus Wallemia mellicola in the intestines of mice enhances the severity of asthma. Wallemia mellicola interacts with the immune system through Dectin-2 expressed on the surface of myeloid and intestinal epithelial cells. Using Dectin-2-deficient mice, we show that the interaction of W.

Targeting Pulmonary Fibrosis by SLC1A5-Dependent Glutamine Transport Blockade.

The neutral amino acid glutamine plays a central role in TGF-β (transforming growth factor-β)-induced myofibroblast activation and differentiation. Cells take up glutamine mainly through a transporter expressed on the cell surface known as solute carrier SLC1A5 (solute carrier transporter 1A5). In the present work, we demonstrated that profibrotic actions of TGF-β are mediated, at least in part, through a metabolic maladaptation of SLC1A5 and that targeting SLC1A5 abrogates multiple facets of fibroblast activation.

CLEC4A and CLEC12B C-type lectin receptors mediate interactions with cell wall components.

C-type lectin receptors (CLRs) are prominently expressed on myeloid cells where they perform multiple functions including serving as pattern recognition receptors (PRRs) to drive innate as well as adaptive immunity to pathogens. Depending on the presence of a tyrosine-based signalling motif, CLR-microbial pathogen engagement may result in either anti- or pro-inflammatory signalling. In this manuscript, we report our laboratory study of two novel CLRs that recognize cell wall homogenates (CWH) and a purified cell wall fraction (CWF).

Dysbiosis of the intestinal fungal microbiota increases lung resident group 2 innate lymphoid cells and is associated with enhanced asthma severity in mice and humans.

Background: The gut-lung axis is the concept that alterations of gut microbiota communities can influence immune function in the lungs. While studies have explored the relationship between intestinal bacterial dysbiosis and asthma development, less is understood about the impact of commensal intestinal fungi on asthma severity and control and underlying mechanisms by which this occurs.

Methods: Wild-type mice were treated with Cefoperazone to deplete gut bacteria and administered Candida albicans or water through gavage.

Preclinical and Toxicology Studies of BRD5529, a Selective Inhibitor of CARD9.

Background: The caspase recruitment domain-containing protein 9 (CARD9) inhibitor BRD5529 has been shown to be an effective in vitro inhibitor of Pneumocystis β-glucan-induced proinflammatory signaling, suggesting its viability as a candidate for preliminary anti-Pneumocystis drug testing in the rodent Pneumocystis pneumonia (PCP) model.

Methods: Mice were injected intraperitoneally (IP) daily with either vehicle or BRD5529 at 0.1 or 1.

Additional C-type lectin receptors mediate interactions with organisms and major surface glycoprotein.

Pathogen-associated molecular patterns' (PAMPs) are microbial signatures that are recognized by host myeloid C-type lectin receptors (CLRs). These CLRs interact with micro-organisms via their carbohydrate recognition domains (CRDs) and engage signalling pathways within the cell resulting in pro-inflammatory and microbicidal responses. In this article, we extend our laboratory study of additional CLRs that recognize fungal ligands against and and their purified major surface glycoproteins (Msgs).

EphA2 Is a Lung Epithelial Cell Receptor for Pneumocystis β-Glucans.

Pneumocystis species interaction with myeloid cells is well known, especially in macrophages; however, how the organism binds to lung epithelial cells is incompletely understood. Ephrin type-A receptor 2 (EphA2) has been previously identified as a lung epithelial pattern recognition receptor that binds to fungal β-glucans. Herein, we also report that EphA2 can also bind Pneumocystis β-glucans, both in isolated forms and also on exposed surfaces of the organism.

Survey of the Transcription Factor Responses of Mouse Lung Alveolar Macrophages to .

is a fungal pathogen that can cause life-threatening infections in individuals who are immunocompromised. Acquired via inhalation, upon entering the respiratory tract, the fungi first encounter innate immune cells such as alveolar macrophages (AMs). Relatively little is known about the AM cellular responses to the organism, and particularly transcription factor (TF) profiles leading to early host responses during infection.

Grading Bleomycin-Induced Pulmonary Fibrosis in ex vivo Mouse Lungs Using Ultrasound Image Analysis.

Objectives: The aim of this study was to assess bleomycin-induced pulmonary fibrosis on ex vivo mouse lungs using ultrasound image grading and texture analysis.

Methods: Excised mouse lungs were divided into 3 groups: control, mild fibrosis, and severe fibrosis based on the monitored indicators of health. B-mode ultrasound images were obtained via scanning the mouse lungs ex vivo.

Building the vertebrate codex using the gene breaking protein trap library.

One key bottleneck in understanding the human genome is the relative under-characterization of 90% of protein coding regions. We report a collection of 1200 transgenic zebrafish strains made with the gene-break transposon (GBT) protein trap to simultaneously report and reversibly knockdown the tagged genes. Protein trap-associated mRFP expression shows previously undocumented expression of 35% and 90% of cloned genes at 2 and 4 days post-fertilization, respectively.

Hexokinase 2 couples glycolysis with the profibrotic actions of TGF-β.

Metabolic dysregulation in fibroblasts is implicated in the profibrotic actions of transforming growth factor-β (TGF-β). Here, we present evidence that hexokinase 2 (HK2) is important for mediating the fibroproliferative activity of TGF-β both in vitro and in vivo. Both Smad-dependent and Smad-independent TGF-β signaling induced HK2 accumulation in murine and human lung fibroblasts through induction of the transcription factor c-Myc.

An ex vivo technique for quantifying mouse lung injury using ultrasound surface wave elastography.

Idiopathic pulmonary fibrosis is a progressively fatal disease with limited treatments. The bleomycin mouse model is often used to simulate the disease process in laboratory studies. The aim of this study was to develop an ex vivo technique for assessing mice lung injury using lung ultrasound surface wave elastography (LUSWE) in the bleomycin mouse model.

Robust activation of microhomology-mediated end joining for precision gene editing applications.

One key problem in precision genome editing is the unpredictable plurality of sequence outcomes at the site of targeted DNA double stranded breaks (DSBs). This is due to the typical activation of the versatile Non-homologous End Joining (NHEJ) pathway. Such unpredictability limits the utility of somatic gene editing for applications including gene therapy and functional genomics.