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H pylori infection causes chronic pancreatitis in Mongolian gerbils

World Journal of Gastroenterology 2007年第29期13卷 3939-3947页

作者： Gabriele Rieder Arno Karnholz Mechthild Stoeckelhuber Juanita L Merchant Rainer Haas max von pettenkofer-institute for hygiene and medical microbiology Ludwig-Maximilians-University 80336 Munich Germany institute of Anatomy Ludwig- Maximilians-University 80336 Munich Germany University of Michigan Departments of Internal Medicine and Molecular and Integrative Physiology Ann Arbor Michigan United States

AIM： To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system. METHODS： Mongolian gerbils were infected with wild type （WT） H pylori type Ⅰ strain B128 or its isogenic mutant B128 △cag γ （defective type Ⅳ secretion）. After seven months of infection, H pylori was reisolated from antrum and corpus and Hpylori DNA was analyzed by seminested polymerase chain reaction （PCR）. Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry. Cytokine mRNA, gastric pH, plasma gastrin, amylase, lipase, and glucose levels were determined. RESULTS： The H pylori infection rate was 95%. Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immuno-histochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals andthose developing transmural inflammation and pancreatitis were significantly increased. Levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue,but not in the pancreas CONCLUSION： H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type Ⅳ secretion system, probably by an indirect mechanism associated with a penetrating ulcer.

关键词： H pylori Mongolian gerbil Pancreatitis Gastritis Penetrating ulcer

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Importance of hydrogenotrophic, aceticlastic and methylotrophic methanogenesis for methane production in terrestrial, aquatic and other anoxic environments: A mini review

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Pedosphere 2020年第1期30卷 25-39页

作者： Ralf CONRAD max Planck institute for Terrestrial microbiology Karl-von-Frisch-Str.10Marburg 35043(Germany)

Microbial methanogenesis is a major source of the greenhouse gas methane(CH4).It is the final step in the anaerobic degradation of organic matter when inorganic electron acceptors such as nitrate,ferric iron,or sulfate have been *** of this degradation pathway is important for the creation of mechanistic models,prediction of future CH4 emission scenarios,and development of mitigation *** most anoxic environments,CH4 is produced from either acetate(aceticlastic methanogenesis)or hydrogen(H2)plus carbon dioxide(CO2)(hydrogenotrophic methanogenesis).Hydrogen can be replaced by other CO2-type methanogenesis,using formate,carbon monoxide(CO),or alcohols as *** ratio of these two pathways is tightly constrained by the stoichiometry of conversion *** the degradation of organic matter is complete(e.g.,degradation of straw in rice paddies),then fermentation eventually results in production of acetate and H2 at a ratio of>67%aceticlastic and<33%hydrogenotrophic ***,acetate production can be favored when heterotrophic or chemolithotrophic acetogenesis is enhanced,and H2 production can be favored when syntrophic acetate oxidation is *** typically occurs at low and elevated temperatures,***,temperature can strongly influence the methanogenic pathway,which may range from 100%aceticlastic methanogenesis at low temperatures to 100%hydrogenotrophic methanogenesis at high ***,if the degradation of organic matter is not complete(e.g.,degradation of soil organic matter),the stoichiometry of fermentation is not tightly constrained,resulting,for example,in the preferential production of H2,followed by hydrogenotrophic *** production of CH4 by either aceticlastic or hydrogenotrophic methanogenesis can also happen if one of the methanogenic substrates is not consumed by methanogens but is,instead,accumulated,volatilized,or utilized *** methano

关键词： electron acceptor fermentation methanogenic pathway organic matter degradation pH soil microbial community temperature Wood-Ljungdahl pathway

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Helicobacter pylori vac A genotype is a predominant determinant of immune response to Helicobacter pylori CagA

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World Journal of Gastroenterology 2017年第26期23卷 4712-4723页

作者： Alexander Link Cosima Langner Wiebke Schirrmeister Wiebke Habendorf Jochen Weigt Marino Venerito Ina Tammer Dirk Schlüter Philipp Schlaermann Thomas F Meyer Thomas Wex Peter Malfertheiner Department of Gastroenterology Hepatology and Infectious DiseasesOtto-von-Guericke University institute of medical microbiology Otto-von-Guericke University Helmholtz Center for Infection Research Department of Molecular Biology Max Planck Institute for Infection Biology Department of Molecular Genetics Medical Laboratory for Clinical ChemistryMicrobiology and Infectious Diseases

To evaluate the frequency of Helicobacter pylori (H. pylori) CagA antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori CagA-immune response. METHODSSystematic data to H. pylori isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile (anti-H. pylori, anti-CagA) was correlated with H. pylori isolates (cagA, EPIYA, vacA s/m genotype), histology (Sydney classification) and mucosal interleukin-8 (IL-8) mRNA and protein expression. Selected H. pylori strains were assessed for H. pylori CagA protein expression and IL-8 induction in co-cultivation model with AGS cells. RESULTSThirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for CagA. Majority of H. pylori isolates were cagA gene positive (93.9%) with following vacA polymorphisms: 42.4% vacA s1m1, 23.2% s1m2 and 34.3% s2m2. Anti-CagA-IgG seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cagA mRNA expression. VacA s and m polymorphisms were the major determinants for positive (vacA s1m1) or negative (vacA s2m2) anti-CagA serological immune response, which also correlated with the in vitro inflammatory potential in AGS cells. In vitro co-cultivation of representative H. pylori strains with AGS cells confirmed functional CagA translocation, which showed only partial correlation with CagA seropositivity in patients, supporting vacA as major co-determinant of the immune response. CONCLUSIONSerological immune response to H. pylori cagA+ strain in H. pylori infected patients is strongly associated with vacA polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.

关键词： Helicobacter pylori Seropositivity Virulence factors CagA VacA Immune response

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The brain–immune cells axis controls tissue specific immunopathology

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Cellular & Molecular Immunology 2019年第2期16卷 101-103页

作者： maxi Heyner Sarah Schreier Andrea Kröger institute for medical microbiology and Hospital hygiene Otto-von-Guericke University MagdeburgMagdeburgGermany Innate Immunity and Infection Group Helmholtz Centre for Infection ResearchBraunschweigGermany

During viral infections,cell death can be induced as a direct result of cytopathic virus replication in various cell types and tissues or as an immune response of the host to the infectious *** leads to an infiltration of inflammatory cells,causing subsequent tissue *** balance between effective elimination of the pathogen and prevention of fatal tissue damage is decisive for *** host has developed various mechanisms to inhibit excessive immune responses.

关键词： prevention damage death

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Cytotoxic innate lymphoid cells sense tumor-derived IL-15: a novel mechanism of cancer immunosurveillance

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3628-3629页

作者： Tobias Franz Jonas Negele Sascha Kahlfuss institute of Molecular and Clinical Immunology Medical FacultyOtto-von-Guericke University MagdeburgMagdeburgGermany institute of medical microbiology and Hospital hygiene Medical FacultyOtto-von-Guericke University MagdeburgMagdeburgGermany Health Campus Immunology Infectiology and Inflammation(GCI3)Medical FacultyOtto-Von-Guericke University MagdeburgMagdeburgGermany Center for Health and medical Prevention(CHaMP) Otto-von-Guericke-UniversityMagdeburgGermany

Recently,Li and colleagues provided in Nature immunology1 a novel mechanism of immunosurveillance in epithelial tumors,in which cytotoxic innate lymphoid cells(ILCs)sense IL-15 secreted by the tumor *** the adaptive immune system,including CD8+cytotoxic lymphocytes(CTLs),and innate immune cells such as Natural Killer(NK)cells are capable of providing antitumor immunity through the release of perforins and *** addition,also cytotoxic group 1 innate lymphoid cells(ILC1s)were reported to exert NK cell-like antitumor cell cytotoxicity.

关键词： lymphoid immunity mechanism

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Add on the next level—the time point of the type I IFN response orchestrates the immune response

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Cellular & Molecular Immunology 2020年第8期17卷 791-793页

作者： Angela Wedekind David Fritzsch Andrea Kröger Research Group Molecular microbiology Institute of Microbiology and Hospital HygieneOtto von Guericke University39120MagdeburgGermany Research Group Innate Immunity and Infection Helmholtz Centre for Infection Research38124BraunschweigGermany

The directed control of an effective cellular or adaptive immune response is the aim of vaccine strategies and tumor *** antibodies prevent the spread of pathogens,while efficient cellular immunotherapy is used to overcome T-cell exhaustion and unresponsiveness toward *** such settings,the type I interferon(IFN)system mediates pleiotropic effects of the immune system that can be either immunostimulating or *** a recent work,De Giovanni et *** a novel regulatory checkpoint by which type I IFN regulates CD4^(+)T-cell *** study dissects the time point of type I IFN induction as a central regulator of the adaptive immune response that determines the balance between humoral and cellular *** findings identify an intriguing and previously undescribed checkpoint that can potentially be manipulated for ***,the authors demonstrate that CD4^(+)T-cell polarization could be influenced by manipulating the IFN response during infection.

关键词： al. vaccine interferon

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IL-33: a jack of all trades in the orchestration of respiratory antibacterial immunity

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Cellular & Molecular Immunology 2017年第11期14卷 875-877页

作者： Julia D Boehme Dunja Bruder Infection Immunology Group Institute of Medical Microbiology and Hospital HygieneOtto-von-Guericke UniversityMagdeburgGermany Immune Regulation Group Department of Immune ControlHelmholtz Centre for Infection ResearchBraunschweigGermany

Influenza A virus(IAV)is the causative agent of mostly mild to moderate seasonal respiratory infections and several pandemic outbreaks,the most recent of which was reported in *** IAV pandemics were associated with an enormous death toll;for example,the 1918 H1N1 pandemic affected hundreds of millions of people globally and resulted in~50 million deaths.1 Microbiologic analyses of patient samples revealed a strong incidence of bacterial pathogens in fatal complications of viral infection.2 To date,many pieces of epidemiologic and experimental evidence reveal pronounced susceptibility to detrimental bacterial superinfection in IAVinfected individuals.

关键词： immunity respiratory hundreds

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Molecular Epidemiology of Nontuberculous Mycobacteria in a German CF Center and Clinical Course of NTM Positive Patients

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Open Journal of medical microbiology 2013年第1期3卷 39-47页

作者： Carolin Kroner Barbara Ganster Matthias Kappler Ann-Christin Grimmelt Bernd H.Belohradsky Michael Hogardt Gudrun Laniado Michael Meissner Soren Schubert Matthias Griese Paediatric Pneumology Dr.von Hauner Children’s HospitalLudwig-Maximilians-UniversityMunichGermany institute for Clinical Chemistry Molecular DiagnosticsMedical Microbiology and Hygiene DepartmentLudwigshafen General HospitalLudwigshafenGermany institute for medical microbiology and Infection Control University HospitalJohann-Wolfgang-Goethe-UniversityFrankfurt/MainGermany max von pettenkofer institute of hygiene and medical microbiology Ludwig-Maximilians-UniversityMunichGermany

Goal of this study was to analyse the clinical course of cystic fibrosis (CF) patients with nontuberculous mycobacteria (NTM) in their respiratory secretions and to investigate the molecular epidemiology of the most prevalent NTM species by multilocus sequence analysis (MLSA). The respiratory specimen and the clinical parameters forced expiratory volume in one second (FEV1), body-mass-index (BMI), erythrocyte sedimentation rate (ESR) 1 h and immunoglobulin G (IgG) of 357 CF patients, 0 - 52.4 years, mean FEV1 2009 81.5% pred were analysed between 1998 and 2010. In 13 patients NTM were detected. 12 of 13 patients carried M. abscessus, for one patient the NTM species was not characterized. 4 patients carried a second NTM species (M. avium, M. chelonae (2x), M. intracellulare). 6 patients exhibited a significant decline in FEV1, however changes in BMI, IgG and ESR were discordant. Molecular genotyping of M. abscessus isolates revealed a unique MLSA pattern in 6 patients. 2 patients harboured identical strains, and one patient a closely related strain. Whether the presence of identical strains is attributed to the acquisition of NTM clones from common environmental sources or to patient-to-patient transmission cannot be definitely clarified. Although cross-in- fection of the three patients with identical/closely related strains in the present cohort is highly unlikely, we recommend strict hygiene measures for all CF patients harbouring NTM.

关键词： Mycobacteria Nontuberculous Mycobacterium abscessus Cystic Fibrosis Molecular Epidemiology Multilocus Sequence Analysis(MLSA) Interferon Gamma

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"Moonlighting" at the power plant: how mitochondria facilitate serial killing by CD8^(+) cytotoxic T cells

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Signal Transduction and Targeted Therapy 2022年第1期7卷 15-16页

作者： Dimitrios Mougiakakos Sascha Kahlfuss Department of Hematology Oncologyand Stem Cell TransplantationOtto-von-Guericke University MagdeburgMagdeburgGermany institute of Molecular and Clinical Immunology Medical FacultyOtto-von-Guericke University MagdeburgMagdeburgGermany institute of medical microbiology and Hospital hygiene Medical FacultyOtto-von-Guericke University MagdeburgMagdeburgGermany Health Campus Immunology InfectiologyInflammation(GC-I3)Medical FacultyOtto-von-Guericke UniversityMagdeburgGermany Center for Health and medical Prevention(CHaMP) Otto-von-Guericke UniversityMagdeburgGermany

Griffiths and colleagues rece ntly dem on strated in Science^(1) that mitochondrial translation is required by CD8^(+)cytotoxic T cells(CTLs)to facilitate serial killing of target ***8^(+)CTLs provide immunity to viruses and tumors by acting as serial killers that eliminate infected or transformed target cells one after *** achieve that,CTLs utilize a cytotoxic protein machinery that involves perforin and granzymes to activate effector caspases and to induce apoptosis in target cells.

关键词： cytotoxic immunity lighting

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The deubiquitinase OTUB1 augments NF-κB-dependent immune responses in dendritic cells in infection and inflammation by stabilizing UBC13

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Cellular & Molecular Immunology 2021年第6期18卷 1512-1527页

作者： Floriana Mulas Xu Wang Shanshan Song Gopala Nishanth Wenjing Yi Anna Brunn Pia-Katharina Larsen Berend Isermann Ulrich Kalinke Antonio Barragan Michael Naumann Martina Deckert Dirk Schlüter institute of medical microbiology and Hospital hygiene Otto-von-Guericke University Magdeburg39120MagdeburgGermany institute of medical microbiology and Hospital Epidemiology Hannover Medical School30625HannoverGermany Chemical Biology Research Center School of Pharmaceutical SciencesWenzhou Medical University325035WenzhouChina Department of Neuropathology Faculty of Medicine and University Hospital CologneUniversity of Cologne50931CologneGermany institute for Experimental Infection Research TWINCORE Centre for Experimental and Clinical Infection Researcha joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research30625HannoverGermany institute for Clinical Chemistry and Pathobiochemistry Otto-von-Guericke University Magdeburg39120MagdeburgGermany Cluster of Excellence-Resolving Infection Susceptibility(RESIST) Hannover Medical School30625HannoverGermany Department of Molecular Biosciences Stockholm University10691StockholmSweden institute for Experimental Internal Medicine Otto-von-Guericke University Magdeburg39120MagdeburgGermany

Dendritic cells(DCs)are indispensable for defense against pathogens but may also contribute to *** of DCs upon the sensing of pathogens by Toll-like receptors(TLRs)is largely mediated by pattern recognition receptor/nuclear factor-κB(NF-κB)signaling and depends on the appropriate ubiquitination of the respective signaling ***,the ubiquitinating and deubiquitinating enzymes involved and their interactions are only incompletely ***,we reveal that the deubiquitinase OTU domain,ubiquitin aldehyde binding 1(OTUB1)is upregulated in DCs upon murine Toxoplasma gondii infection and lipopolysaccharide *** of DCs with the TLR11/12 ligand *** profilin and the TLR4 ligand lipopolysaccharide induced an increase in NF-κB activation in OTUB1-competent cells,resulting in elevated interleukin-6(IL-6),IL-12,and tumor necrosis factor(TNF)production,which was also observed upon the specific stimulation of TLR2,TLR3,TLR7,and ***,OTUB1 promoted NF-κB activity in DCs by K48-linked deubiquitination and stabilization of the E2-conjugating enzyme UBC13,resulting in increased K63-linked ubiquitination of IRAK1(IL-1 receptor-associated kinase 1)and TRAF6(TNF receptor-associated factor 6).Consequently,DC-specific deletion of OTUB1 impaired the production of cytokines,in particular IL-12,by DCs over the first 2 days of *** infection,resulting in the diminished production of protective interferon-γ(IFN-γ)by natural killer cells,impaired control of parasite replication,and,finally,death from chronic ***,all of which could be prevented by low-dose IL-12 treatment in the first 3 days of *** contrast,impaired OTUB1-deficient DC activation and cytokine production by OTUB1-deficient DCs protected mice from lipopolysaccharide-induced ***,these findings identify OTUB1 as a potent novel regulator of DCs during infectious and inflammatory diseases.

关键词： OTUB1 dendritic cell signal transduction ubiquitination innate immunity

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