136 results match your criteria: "Institute for Experimental Immunology and Imaging[Affiliation]"

Neutrophils provide first line of host defense against bacterial infections utilizing glycolysis for their effector functions. How glycolysis and its major byproduct lactate are triggered in bone marrow (BM) neutrophils and their contribution to neutrophil mobilization in acute inflammation is not clear. Here we report that bacterial lipopolysaccharides (LPS) or Salmonella Typhimurium triggers lactate release by increasing glycolysis, NADPH-oxidase-mediated reactive oxygen species and HIF-1α levels in BM neutrophils.

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Defective migration and dysmorphology of neutrophil granulocytes in atypical chronic myeloid leukemia treated with ruxolitinib.

BMC Cancer

July 2020

Department of Hematology, University Hospital, West German Cancer Center (WTZ), University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany.

Article Synopsis
  • Researchers studied a 69-year-old man with a rare type of leukemia called atypical chronic myeloid leukemia (aCML) to see how his white blood cells (neutrophils) moved and worked.
  • They found that, even after treatment, his neutrophils had trouble moving properly and looked different compared to healthy cells.
  • After starting a new medicine called ruxolitinib, the shape of his neutrophils got better, but their movement didn’t improve, and they noticed a change in the type of mutations in the cells.
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Durable and controlled depletion of neutrophils in mice.

Nat Commun

June 2020

Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland.

Neutrophils are an essential part of the innate immune system. To study their importance, experimental studies often aim to deplete these cells, generally by injecting anti-Ly6G or anti-Gr1 antibodies. However, these approaches are only partially effective, transient or lack specificity.

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Systemic but not MDSC-specific IRF4 deficiency promotes an immunosuppressed tumor microenvironment in a murine pancreatic cancer model.

Cancer Immunol Immunother

October 2020

Center of Integrated Protein Science Munich (CIPSM) and Division of Clinical Pharmacology, University Hospital, LMU Munich, Munich, Germany.

Pancreatic ductal adenocarcinoma is characterized by a strong immunosuppressive network with a dense infiltration of myeloid cells including myeloid-derived suppressor cells (MDSC). Two distinct populations of MDSC have been defined: polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC). Several factors influence the development and function of MDSC including the transcription factor interferon regulatory factor 4 (IRF4).

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Article Synopsis
  • Cell migration research is a rapidly growing field, but current datasets are underutilized due to varying experimental methods and formats that hinder data sharing and analysis.
  • Making these datasets findable, accessible, interoperable, and reusable (FAIR) would enhance opportunities for meta-analysis and data integration.
  • The Cell Migration Standardisation Organisation (CMSO) is working to establish standardized formats and vocabularies for cell migration data, which will improve algorithms, tools, and enable further exploration of this complex biological process.
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In retroviral infections, different immunological mechanisms are involved in the development of a chronic infection. In the Friend virus (FV) model, regulatory T cells (Tregs) were found to induce CD8 T cell dysfunction before viral clearance is achieved and thus contribute to viral chronicity. Although studied for decades, the exact suppressive mechanisms of Tregs in the FV model remain elusive and an unavailable therapeutic target.

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The ability of vaccines to induce T cell responses is crucial for preventing diseases caused by viruses. Nanoparticles (NPs) are considered to be efficient tools for the initiation of potent immune responses. Calcium phosphate (CaP) NPs are a class of biodegradable nanocarriers that are able to deliver immune activating molecules across physiological barriers.

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is an opportunistic fungal pathogen that can cause life-threatening invasive lung infections in immunodeficient patients. The cellular and molecular processes of infection during onset, establishment, and progression of infections are highly complex and depend on both fungal attributes and the immune status of the host. Therefore, preclinical animal models are of paramount importance to investigate and gain better insight into the infection process.

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In vivo two-photon imaging is a valuable technique for studies of viral pathogenesis and host responses to infection in vivo. In this protocol, we describe a methodology for analyzing influenza virus-infected lung in vivo by two-photon imaging microscopy. We describe the surgical procedure, how to stabilize the lung, and an approach to analyzing the data.

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Periprosthetic infection (PPI) is a devastating complication in joint replacement surgery. On the background of an aging population, the number of joint replacements and associated complications is expected to increase. The capability for biofilm formation and the increasing resistance of different microbes to antibiotics have complicated the treatment of PPI, requiring the need for the development of alternative treatment options.

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A high intratumoral frequency of neutrophils is associated with poor clinical outcome in most cancer entities. It is hypothesized that immunosuppressive MDSC (myeloid-derived suppressor cell) activity of neutrophils against tumor-reactive T cells contributes to this effect. However, direct evidence for such activity in situ is lacking.

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Closed circulatory systems (CCS) underlie the function of vertebrate organs, but in long bones their structure is unclear, although they constitute the exit route for bone marrow (BM) leukocytes. To understand neutrophil emigration from BM, we studied the vascular system of murine long bones. Here we show that hundreds of capillaries originate in BM, cross murine cortical bone perpendicularly along the shaft and connect to the periosteal circulation.

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Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis.

Cancer Cell

September 2019

Cancer Research UK Beatson Institute, Glasgow, UK; Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, UK. Electronic address:

The metastatic process of colorectal cancer (CRC) is not fully understood and effective therapies are lacking. We show that activation of NOTCH1 signaling in the murine intestinal epithelium leads to highly penetrant metastasis (100% metastasis; with >80% liver metastases) in Kras-driven serrated cancer. Transcriptional profiling reveals that epithelial NOTCH1 signaling creates a tumor microenvironment (TME) reminiscent of poorly prognostic human CRC subtypes (CMS4 and CRIS-B), and drives metastasis through transforming growth factor (TGF) β-dependent neutrophil recruitment.

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Next-generation imaging of the skeletal system and its blood supply.

Nat Rev Rheumatol

September 2019

Institute for Experimental Immunology and Imaging, University Hospital, University Duisburg-Essen, Essen, Germany.

Bone is organized in a hierarchical 3D architecture. Traditionally, analysis of the skeletal system was based on bone mass assessment by radiographic methods or on the examination of bone structure by 2D histological sections. Advanced imaging technologies and big data analysis now enable the unprecedented examination of bone and provide new insights into its 3D macrostructure and microstructure.

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Across a majority of cancer types tumor-associated neutrophils (TAN) are linked with poor prognosis. However, the underlying mechanisms, especially the intratumoral behavior of TAN, are largely unknown. Using intravital multiphoton imaging on a mouse model with neutrophil-specific fluorescence, we measured the migration of TAN in distinct compartments of solid tumor cell lesions .

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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Cardioprotection by salvage of the infarct-affected myocardium is an unmet yet highly desired therapeutic goal. To develop new dedicated therapies, experimental myocardial ischemia/reperfusion (I/R) injury would require methods to simultaneously characterize extent and localization of the damage and the ensuing inflammatory responses in whole hearts over time. Here we present a three-dimensional (3D), simultaneous quantitative investigation of key I/R injury-components by combining bleaching-augmented solvent-based non-toxic clearing (BALANCE) using ethyl cinnamate (ECi) with light sheet fluorescence microscopy.

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Location of Neutrophils in Different Compartments of the Damaged Mouse Brain After Severe Ischemia/Reperfusion.

Stroke

June 2019

From the Department of Brain Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona (IIBB)-Consejo Superior de Investigaciones Científicas (CSIC), Spain (A.O.-d.-A., M. Gallizioli, J.P., C.J., A.S.-P., A.M.P.).

Background and Purpose- Ischemia attracts neutrophils to the injured brain. However, neutrophil location and access to the damaged brain tissue is not yet entirely understood. We aimed to investigate neutrophil location in a mouse model of cerebral ischemia/reperfusion.

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The perpetuation of inflammation is an important pathophysiological contributor to the global medical burden. Chronic inflammation is promoted by non-programmed cell death; however, how inflammation is instigated, its cellular and molecular mediators, and its therapeutic value are poorly defined. Here we use mouse models of atherosclerosis-a major underlying cause of mortality worldwide-to demonstrate that extracellular histone H4-mediated membrane lysis of smooth muscle cells (SMCs) triggers arterial tissue damage and inflammation.

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The prognostic value of sentinel lymph nodes on distant metastasis-free survival in patients with high-risk squamous cell carcinoma.

Eur J Cancer

April 2019

Department of Dermatology, Venerology and Allergology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; West German Cancer Center, University Duisburg-Essen, 45122 Essen, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany. Electronic address:

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common cutaneous cancer worldwide. Several tumour characteristics are considered to pose an elevated risk for systemic spread of carcinoma cells ('high-risk' features). Early detection of subclinical metastases could permit early treatment and improve overall survival.

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B cell follicles of the spleen and lymph nodes are immune privileged sites and serve as sanctuaries for infected CD4 cells in HIV infection. It is assumed that CD8 T cell responses promote the establishment of the reservoir, as B cell follicles do not permit CD8 T cell entry. Here we analyzed the infected cell population in the Friend retrovirus (FV) infection and investigated whether FV can similarly infect follicular cells.

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Hepatitis B virus (HBV) replication and envelopment is dependent on cellular autophagy. Previously, we have provided evidence for the extensive lysosomal degradation of HBV virions and the hepatitis B surface antigen (HBsAg), which is likely controlled by autophagosome-lysosome fusion. Synaptosomal-associated protein 29 (SNAP29) has been identified as a protein specifically mediating autophagosome-lysosome fusion.

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Antibody ligation of the murine neutrophil surface protein Ly6G disrupts neutrophil migration in some contexts but not others. We tested whether this variability reflected divergent dependence of neutrophil migration on β2 integrins, adhesion molecules that interact with Ly6G at the neutrophil surface. In integrin-dependent murine arthritis, Ly6G ligation attenuated joint inflammation, even though mice lacking Ly6G altogether developed arthritis normally.

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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.

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