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Mast cells as rapid innate sensors of cytomegalovirus by TLR3/TRIF signaling-dependent and -independent mechanisms

Cellular & Molecular Immunology 2015年第2期12卷 192-201页

作者： Marc Becker Niels AW Lemmermann stefan ebert Pamela Baars Angelique Renzaho Jurgen Podlech Michael Stassen Matthias J Reddehase Institute for Immunology Research Center for Immunotherapy (FZI) at the University Medical Center of the Johannes Gutenberg University Mainz Germany Institute for Virology Research Center for Immunotherapy (FZI) at the University Medical Center of the Johannes Gutenberg University Mainz Germany These authors contributed equally to this work Co-senior authors

The succinct metaphor,‘the immune system＇s loaded gun＇, has been used to describe the role of mast cells （MCs） due to their storage of a wide range of potent pro-inflammatory and antimicrobial mediators in secretory granules that can be released almost instantly on demand to fight invaders. Located at host-environment boundaries and equipped with an arsenal of pattern recognition receptors, MCs are destined to be rapid innate sensors of pathogens penetrating endothelial and epithelial surfaces. Although the importance of MCs in antimicrobial and antiparasitic defense has long been appreciated, their role in raising the alarm against viral infections has been noted only recently. Work on cytomegalovirus （CMV） infection in the murine model has revealed MCs as players in a novel cross-talk axis between innate and adaptive immune surveillance of CMV, in that infection of MCs, which is associated with MC degranulation and release of the chemokine CCL5, enhances the recruitment of protective CD8 T cells to extravascular sites of virus replication, specifically to lung interstitium and alveolar epithelium. Here, we have expanded on these studies by investigating the conditions for MC activation and the consequent degranulation in response to host infection. Surprisingly, the data revealed two temporally and mechanistically distinct waves of MC activation： an almost instant indirect activation that depended on TLR3/TRIF signaling and delayed activation by direct infection of MCs that did not involve TLR3/rRIF signaling. Cell type-specific Cre-recombination that yielded eGFP-expressing reporter virus selectively originating from MCs identified MC as a new in vivo, first-hit target cell of productive murine CMV infection.

关键词： cytomegalovirus innate immunity mast cells mast cell-specific Cre-recombination TLR3FrRIF-signaling

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Prevalence of H pylori associated 'high risk gastritis' for development of gastric cancer in patients with normal endoscopic findings

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World Journal of Gastroenterology 2006年第34期12卷 5509-5512页

作者： Andreas Leodolter Matthias P ebert Ulrich Peitz Kathlen Wolle stefan Kahl Michael Vieth Peter Malfertheiner Department of Gastroenterology and Hepatology Otto-von-Guericke University Magdeburg Leipziger Street 44 Magdeburg 39120 Germany Institute of Pathology Otto-von-Guericke University Magdeburg Leipziger Street 44 Magdeburg 39120 Germany

AIM： To investigate the prevalence of H pylori associated corpus-predominant gastritis （CPG） or pangastritis, severe atrophy, and intestinal metaplasia （IM） in patients without any significant abnormal findings during upper- GI endoscopy. METHODS： Gastric biopsies from 3548 patients were obtained during upper GI-endoscopy in a 4-year period. Two biopsies from antrum and corpus were histologically assessed according to the updated Sydney-System. Eight hundred and forty-five patients （mean age 54.8 ± 2.8 years） with H pylori infection and no peptic ulcer or abnormal gross findings in the stomach were identified and analyzed according to gastritis phenotypes using different scodng systems. RESULTS： The prevalence of severe H pylori associated changes like pangastritis, CPG, IN, and severe atrophy increased with age, reaching a level of 20% in patients of the age group over 45 years. No differences in frequencies between genders were observed. The prevalence of IM had the highest increase, being 4-fold higher at the age of 65 years versus in individuals less than 45 years. CONCLUSION： The prevalence of gastritis featuring at risk for cancer development increases with age. These findings reinforce the necessity for the histological assessment, even in subjects with normal endoscopic appearance. The age-dependent increase in prevalence of severe histopathological changes in gastric mucosa, however, does not allow estimating the individual risk for gastric cancer development-only a proper follow-up can provide this information.

关键词： H pylori Gastric cancer Gastritis

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Breath and string test: A diagnostic package for the identification of treatment failure and antibiotic resistance of Helicobacter pylori without the necessity of upper gastrointestinal endoscopy

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World Journal of Gastroenterology 2005年第4期11卷 584-586页

作者： Andreas Leodolter Kathlen Wolle Ulrike von Arnim stefan Kahl Gerhard Treiber Matthias P.ebert Ulrich Peitz Peter Malfertheiner Department of Gastroenterology Hepatology and Infectious Diseases University of MagdeburgGermany

AIM: Helicobacter pylori (H pylori) resistance after failed eradication has a major impact on the outcome of a further treatment regimen. The aim of this study was to assess the validity of a non-invasive strategy using the 13C-urea breath test (UBT) and the gastric string test in identifying post-treatment resistance of H pylori. METHODS: The UBT was routinely performed 4 to 6 wk after H pylori eradication therapy. Forty-two patients (24 females, 18 males, mean age 48 years) with a positive UBT were included in the study. A gastric string test using a capsule containing a 90 cm-long nylon fiber was performed. Before the capsule was swallowed, the free end of the string was taped to the cheek. After one hour in the stomach, the string was withdrawn. The distal 20 cm of the string was inoculated onto an agar plate and processed under micro-aerophilic conditions. Following the string test, upper gastrointestinal endoscopy was performed to obtain gastric biopsies for conventional culture. RESULTS: H pylori was successfully cultured from the gastric string in 34 patients (81%), but not in 5 patients due to contamination with oropharyngeal flora. H py/oriwas cultured from the gastric biopsies obtained at endoscopy in 39 patients (93%). CONCLUSION: The UBT followed by the gastric string test in the case of treatment failure is a valid diagnostic strategy with the aim of determining the post-therapeutic antibiotic resistance of H pylori with little inconvenience to the patient. Upper Gl-endoscopy can be avoided in several cases by applying consequently this diagnostic package.

关键词： Helicobacter pylorr, Antibiotic resistance 13C-urea breath test Gastric string test

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Interdisciplinary management of central nervous system metastasis and neoplastic meningitis:recent developments and future perspectives

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Journal of Cancer Metastasis and Treatment 2016年第1期2卷 163-175页

作者： Ghazaleh Tabatabai Marilin Koch Cristiana Roggia Juliane ebert Claus Garbe Friedegund Meier Sara Brucker Eva Maria Grischke Diethelm Wallwiener Robert Möhle Lothar Kanz Walter Erich Aulitzky Ulrike Ernemann Christian laFougere Konstantin Nikolaou Bernd Pichler Jens Schittenhelm Manuela Neumann Falko Fend stefan Czemmel Sven Nahnsen Frank Paulsen Daniel Zips Maike van Lessen Hans-Otto Karnath Ulf Ziemann Constantin Roder Marco Skardelly Jürgen Bernd Honegger Marcos Tatagiba Interdisciplinary Division of Neuro-Oncology Departments of Vascular Neurology and NeurosurgeryUniversity Hospital TübingenHertie Institute for Clinical Brain ResearchEberhard Karls University72076 TübingenGermany Division of Dermato-Oncology Department of DermatologyUniversity Hospital TübingenEberhard Karls University72076 TübingenGermany Department of Gynecology and Ostetrics University Hospital TübingenEberhard Karls University72076 TübingenGermany Department of Internal Medicine(II) University Hospital TübingenEberhard Karls University72076 TübingenGermany Department of Hematology and Oncology Robert Bosch Hospital StuttgartStuttgartGermanyComprehensive Cancer CenterTübingen StuttgartGermany Department of Diagnostic and Interventional Neuroradiology University Hospital TübingenEberhard Karls University72076 TübingenGermany Department of Nuclear Medicine University Hospital TübingenEberhard Karls University72076 TübingenGermany Department of Diagnostic and Interventional Radiology University Hospital TübingenEberhard Karls University72076 TübingenGermany Department of Preclinical Imaging and Radiopharmacy University Hospital TübingenEberhard Karls University72076 TübingenGermany Department of Pathology and Neuropathology University Hospital TübingenEberhard Karls University72076 TübingenGermany Department of Radiation Oncology University Hospital TübingenEberhard Karls University72076 TübingenGermany Division of Neuropsychology University Hospital TübingenHertie Institute for Clinical Brain ResearchEberhard Karls University72076 TübingenGermany Center for CNS tumors Comprehensive Cancer Center Tübingen StuttgartGermany Center for Personalized Medicine University Hospital TübingenEberhard Karls UniversityTübingenGermany Center for Dermato-Oncology University Hospital DresdenGermany Quantitative Biology Center(QBiC) Eberhard Karls UniversityTübingenGermany DKTK DKFZ partner site Tübingen.18Department of ImmunologyEberhard Karls University TübingenGermany

The incidence of metastatic disease in the central nervous system(CNS)is *** to current estimates,up to a third of adult cancer patients will suffer from CNS *** evidence-based data from prospective randomized trials are rare,however,because CNS metastasis patients were often excluded from clinical trial *** management of CNS metastasis patients is therefore rather ill-defined and an interdisciplinary *** basic and translational science data have begun contributing to a more profound understanding of the molecular mechanisms leading to invasion of tumor cells into the *** report reviews advances,challenges,and perspectives in this field.

关键词： Brain tumor central nervous system metastases interdisciplinary management

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