Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer.

Chronic inflammation drives the progression of colorectal cancer (CRC). Increased expression of interleukin (IL)-17A is associated with poor prognosis, and IL-17A blockade curbs tumor progression in preclinical models of CRC. Here we examined the impact of IL-1 signaling, a key regulator of the IL-17 pathway, in different cell types within the CRC microenvironment.

Microglial cell loss after ischemic stroke favors brain neutrophil accumulation.

Stroke attracts neutrophils to the injured brain tissue where they can damage the integrity of the blood-brain barrier and exacerbate the lesion. However, the mechanisms involved in neutrophil transmigration, location and accumulation in the ischemic brain are not fully elucidated. Neutrophils can reach the perivascular spaces of brain vessels after crossing the endothelial cell layer and endothelial basal lamina of post-capillary venules, or migrating from the leptomeninges following pial vessel extravasation and/or a suggested translocation from the skull bone marrow.

Biomolecule-corona formation confers resistance of bacteria to nanoparticle-induced killing: Implications for the design of improved nanoantibiotics.

Multidrug-resistant bacterial infections are a global health threat. Nanoparticles are thus investigated as novel antibacterial agents for clinical practice, including wound dressings and implants. We report that nanoparticles' bactericidal activity strongly depends on their physical binding to pathogens, including multidrug-resistant primary clinical isolates, such as Staphylococcus aureus, Klebsiella pneumoniae or Enterococcus faecalis.

Surveillance of Myelodysplastic Syndrome via Migration Analyses of Blood Neutrophils: A Potential Prognostic Tool.

Autonomous migration is a central characteristic of immune cells, and changes in this function have been correlated to the progression and severity of diseases. Hence, the identification of pathologically altered leukocyte migration patterns might be a promising approach for disease surveillance and prognostic scoring. However, because of the lack of standardized and robust assays, migration patterns have not been clinically exploited so far.

Myeloid-derived suppressor cells control B cell accumulation in the central nervous system during autoimmunity.

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) have been characterized in the context of malignancies. Here we show that PMN-MDSCs can restrain B cell accumulation during central nervous system (CNS) autoimmunity. Ly6G cells were recruited to the CNS during experimental autoimmune encephalomyelitis (EAE), interacted with B cells that produced the cytokines GM-CSF and interleukin-6 (IL-6), and acquired properties of PMN-MDSCs in the CNS in a manner dependent on the signal transducer STAT3.

Neutrophils instruct homeostatic and pathological states in naive tissues.

Immune protection relies on the capacity of neutrophils to infiltrate challenged tissues. Naive tissues, in contrast, are believed to remain free of these cells and protected from their toxic cargo. Here, we show that neutrophils are endowed with the capacity to infiltrate multiple tissues in the steady-state, a process that follows tissue-specific dynamics.

A systematic electron microscopic study on the uptake of barium sulphate nano-, submicro-, microparticles by bone marrow-derived phagocytosing cells.

Nanoparticles can act as transporters for synthetic molecules and biomolecules into cells, also in immunology. Antigen-presenting cells like dendritic cells are important targets for immunotherapy in nanomedicine. Therefore, we have used primary murine bone marrow-derived phagocytosing cells (bmPCs), i.

Noninflammatory Diffuse Follicular Hypertrophy/Hyperplasia of Graves Disease: Morphometric Evaluation in an Experimental Mouse Model.

Objectives: Experimental models of Graves hyperthyroid disease accompanied by Graves orbitopathy (GO) can be efficiently induced in susceptible inbred strains of mice by immunization by electroporation of heterologous human TSH receptor (TSHR) A-subunit plasmid. The interrelated pathological findings in the thyroid glands of Graves disease (GD) that explain the core changes classically include diffuse follicular hyperplasia and multifocal mild lymphocytic infiltrate. However, the relative contributions of different thyroid tissue components (colloid, follicular cells, and stroma) have not been previously evaluated.

Modeling Hemolytic-Uremic Syndrome: In-Depth Characterization of Distinct Murine Models Reflecting Different Features of Human Disease.

Diarrhea-positive hemolytic-uremic syndrome (HUS) is a renal disorder that results from infections with Shiga-toxin (Stx)-producing . The aim of this study was to establish well-defined refined murine models of HUS that can serve as preclinical tools to elucidate molecular mechanisms of disease development. C57BL/6J mice were subjected to different doses of Stx2 purified from an O157:H7 patient isolate.

Nanoparticle decoration impacts airborne fungal pathobiology.

Airborne fungal pathogens, predominantly , can cause severe respiratory tract diseases. Here we show that in environments, fungal spores can already be decorated with nanoparticles. Using representative controlled nanoparticle models, we demonstrate that various nanoparticles, but not microparticles, rapidly and stably associate with spores, without specific functionalization.

Beware the intruder: Real time observation of infiltrated neutrophils and neutrophil-Microglia interaction during stroke in vivo.

Inflammation plays an important role in the pathogenesis of ischemic stroke including an acute and prolonged inflammatory process. The role of neutrophil granulocytes as first driver of the immune reaction from the blood site is under debate due to controversial findings. In bone marrow chimeric mice we were able to study the dynamics of tdTomato-expressing neutrophils and GFP-expressing microglia after photothrombosis using intravital two-photon microscopy.

Respiratory Influenza A Virus Infection Triggers Local and Systemic Natural Killer Cell Activation Toll-Like Receptor 7.

The innate immune system senses influenza A virus (IAV) through different pathogen-recognition receptors including Toll-like receptor 7 (TLR7). Downstream of viral recognition natural killer (NK) cells are activated as part of the anti-IAV immune response. Despite the known decisive role of TLR7 for NK cell activation by therapeutic immunostimulatory RNAs, the contribution of TLR7 to the NK cell response following IAV infection has not been addressed.

Imaging of cytotoxic antiviral immunity while considering the 3R principle of animal research.

Unlabelled: Adoptive cell transfer approaches for antigen-specific CD8 T cells are used widely to study their effector potential during infections or cancer. However, contemporary methodological adaptations regarding transferred cell numbers, advanced imaging, and the 3R principle of animal research have been largely omitted. Here, we introduce an improved cell transfer method that reduces the number of donor animals substantially and fulfills the requirements for intravital imaging under physiological conditions.

ICAM1+ neutrophils promote chronic inflammation via ASPRV1 in B cell-dependent autoimmune encephalomyelitis.

Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive to date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during experimental autoimmune encephalomyelitis (EAE). Transcriptomic analysis of these 2 subpopulations indicated that neutrophils, once extravasated, acquire macrophage-like properties, including the potential for immunostimulation and MHC class II-mediated antigen presentation.

Visualizing the function and fate of neutrophils in sterile injury and repair.

Neutrophils have been implicated as harmful cells in a variety of inappropriate inflammatory conditions where they injure the host, leading to the death of the neutrophils and their subsequent phagocytosis by monocytes and macrophages. Here we show that in a fully repairing sterile thermal hepatic injury, neutrophils also penetrate the injury site and perform the critical tasks of dismantling injured vessels and creating channels for new vascular regrowth. Upon completion of these tasks, they neither die at the injury site nor are phagocytosed.

Quantitative Analysis of Proteome Modulations in Alveolar Epithelial Type II Cells in Response to Pulmonary Infection.

The ubiquitous mold threatens immunosuppressed patients as inducer of lethal invasive aspergillosis. conidia are airborne and reach the alveoli, where they encounter alveolar epithelial cells (AEC). Previous studies reported the importance of the surfactant-producing AEC II during infection experiments using cell lines.

Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Lung Infections .

Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy or bone marrow transplant patients caused by the ubiquitous environmental fungus . Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI) using a [Cu]DOTA-labeled mouse monoclonal antibody (mAb), mJF5, specific to .

Frontline Science: Proliferation of Ly6C monocytes during urinary tract infections is regulated by IL-6 trans-signaling.

Ly6C monocytes are important components of the innate immune defense against infections. These cells have been shown to proliferate in the bone marrow of mice with systemic infections. However, the proliferative capacity of Ly6C monocytes in infected peripheral tissues as well as the associated regulatory mechanisms remain unclear.

Quantitative Visualization of Leukocyte Infiltrate in a Murine Model of Fulminant Myocarditis by Light Sheet Microscopy.

Light-sheet fluorescence microscopy (LSFM), in combination with chemical clearing protocols, has become the gold standard for analyzing fluorescently labelled structures in large biological specimens, and is down to cellular resolution. Meanwhile, the constant refinement of underlying protocols and the enhanced availability of specialized commercial systems enable us to investigate the microstructure of whole mouse organs and even allow for the characterization of cellular behavior in various live-cell imaging approaches. Here, we describe a protocol for the spatial whole-mount visualization and quantification of the CD45 leukocyte population in inflamed mouse hearts.

3D visualization and quantification of microvessels in the whole ischemic mouse brain using solvent-based clearing and light sheet microscopy.

The visualization of cerebral microvessels is essential for understanding brain remodeling after stroke. Injection of dyes allows for the evaluation of perfused vessels, but has limitations related either to incomplete microvascular filling or leakage. In conventional histochemistry, the analysis of microvessels is limited to 2D structures, with apparent limitations regarding the interpretation of vascular circuits.

Resident macrophages in the healthy and inflamed intestinal muscularis externa.

Macrophages reside in a dense cellular network in the intestinal muscularis externa, and there is emerging evidence that the functionality of these cells determines the local microenvironment. Inflammatory responses during intestinal diseases change the homeostatic functionality of these cells causing inflammation and intestinal dysmotility. Such disturbances are not only induced by a change in the cellular composition in the intestinal muscularis but also by an altered crosstalk with the peripheral and central nervous system.