Single cell preparations of Mycobacterium tuberculosis damage the mycobacterial envelope and disrupt macrophage interactions

For decades, investigators have studied the interaction o

L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis

Macrophage adhesion and stretching have been shown to induce interleukin (IL)-1β production, but the mechanism of this mechanotransduction remains unclear. Here we specify the molecular link between mechanical tension on tissue-resident macrophages and activation of the NLRP3 inflammasome, which governs IL-1β production. NLRP3 activation enhances antimicrobial defense, but excessive NLRP3 activity causes inflammatory tissue damage in conditions such as pulmonary fibrosis and acute respiratory distress syndrome. We find that the actin-bundling protein L-plastin (LPL) significantly enhances NLRP3 assembly. Specifically, LPL enables apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) oligomerization during NLRP3 assembly by stabilizing ASC interactions with the kinase Pyk2, a component of cell-surface adhesive structures called podosomes. Upon treatment with exogenous NLRP3 activators, lung-resident alveolar macrophages (AMs) lacking LPL exhibit reduced caspase-1 activity, IL-1β cleavage, and gasdermin-D processing. LP

Current Perspective on In Vivo Molecular Imaging of Immune Cells

Contemporaneous development of improved immune cell-based therapies, and powerful imaging tools, has prompted growth in technologies for immune cell tracking in vivo. Over the past couple of decades, imaging tools such as magnetic resonance imaging (MRI) and optical imaging have successfully monitored the trafficking patterns of therapeutic immune cells and assisted the evaluation of the success or failure of immunotherapy. Recent advancements in imaging technology have made imaging an indispensable module of immune cell-based therapies. In this review, emerging applications of non-radiation imaging modalities for the tracking of a range of immune cells are discussed. Applications of MRI, NIR, and other imaging tools have demonstrated the potential of non-invasively surveying the fate of both phagocytic and non-phagocytic immune cells in vivo

Comparison of Transradial and Transfemoral Access for Coronary Bypass Graft Angiography

Introduction: Transradial access has been shown to be safe and effective in the setting of percutaneous coronary intervention (PCI) and even being benefi cial in regards to vascular complications and perceived quality of life after the intervention. However, data is limited in patients having previously undergone coronary artery bypass grafting (CABG) where procedural complexity can be increased.Methods: Studies comparing transradial and transfemoral access for PCI in patients having undergone CABG were identifi ed. Data for similar endpoints was extracted for subsequent meta-analysis. Bias and heterogeneity were also assessed. Results: There was no significant difference in procedure success (OR 0.87, 95% CI 0.43 to 1.73, p=0.68), procedure time (MD 231.98 seconds, 95% CI -84.39 to 548.36, p=0.15), fl uoroscopy time (MD 51.75 seconds, 95% CI -66.83 to 170.34, p=0.39), contrast volume (MD 1.67 milliliter, 95% CI -22.16 to 25.49, p = 0.89) and in-hospital mortality (OR 0.50, 95% CI 0.13 to 1.92, p=0.31) between those in the transradial and transfemoral access groups. Transradial access was associated with fewer vascular complications (OR 0.33, 95% CI 0.16 to 0.72, p=0.005). Conclusions: Transradial access for PCI in patients with prior CABG is safe, with fewer vascular complications, and offers an effective and potentially favorable alternative to transfemoral access.Condensed abstract: Transradial access has been demonstrated to offer benefi ts in comparison to transfemoral access for percutaneous coronary intervention (PCI). This advantage has not been fully elucidated for PCI of coronary artery bypass grafts (CABG). A meta-analysis was conducted to study the two access options and found that transradial access for PCI of CABG grafts is safe and may in fact be associated with fewer vascular complications.</p

High-resolution imaging of protein secretion at the single-cell level using plasmon-enhanced FluoroDOT assay

Secreted proteins mediate essential physiological processes. With conventional assays, it is challenging to map the spatial distribution of proteins secreted by single cells, to study cell-to-cell heterogeneity in secretion, or to detect proteins of low abundance or incipient secretion. Here, we introduce the "FluoroDOT assay," which uses an ultrabright nanoparticle plasmonic-fluor that enables high-resolution imaging of protein secretion. We find that plasmonic-fluors are 16,000-fold brighter, with nearly 30-fold higher signal-to-noise compared with conventional fluorescence labels. We demonstrate high-resolution imaging of different secreted cytokines in the single-plexed and spectrally multiplexed FluoroDOT assay that revealed cellular heterogeneity in secretion of multiple proteins simultaneously. Using diverse biochemical stimuli, including Mycobacterium tuberculosis infection, and a variety of immune cells such as macrophages, dendritic cells (DCs), and DC-T cell co-culture, we demonstrate that the assay is versatile, facile, and widely adaptable for enhancing biological understanding of spatial and temporal dynamics of single-cell secretome