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The role of the immune system in the intestine after an infection with Salmonella Typhimurium |
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Kathrin Endt |
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The gram negative bacterium Salmonella Typhimurium is a major cause of bacterial food-borne disease with 1.3 billion cases world wide per year and more than a million annual deaths. The bacterium is known to induce severe gastrointestinal inflammation by colonizing the gut and invading intestinal tissues. This leads to a complex network of interactions between the pathogenic bacterium, the intestinal epithelium, the commensals and the immune system. Generally, the symptoms of the acute infection last for 3-5 days the pathogen is subsequently cleared by the immune system. So far, there is no vaccine available to prevent the disease.
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The main research in the lab of Wolf-Dietrich Hardt focuses on processes involved in the inflammation of the intestine after an infection with Salmonella. To trigger intestinal inflammation S. Typhimurium possesses a number of different virulence factors that influence biological functions of the host. The bacterium can deliver virulence-associated effector proteins directly into host cells via molecular syringes, so called type three secretion systems (TTSS), which mediate bacterial invasion into gut epithelium and replication within the gut tissue.
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While Salmonella Typhimurium causes a self-limiting inflammation of the intestine (enterocolitis) in humans, mice do not develop an inflammation. To study the mucosal immune response upon Salmonella infection the group of Wolf-Dietrich Hardt has therefore developed a streptomycin pretreated mouse model. Administration of the antibiotic streptomycin to mice overcomes the phenomenon of “colonization resistance” and enables Salmonella to colonize the intestine and to cause severe inflammation. In this model, oral infection with a S. Typhimurium leads to intestinal inflammation, which allows us to study the bacterial virulence factors and the elements of the host’s immune system contributing to disease.
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Recently, studies in the streptomycin pretreated mouse model have identified S. Typhimurium mutants which summarize the different steps of the acute human infection: colonization, acute inflammation and clearance of the pathogen after approximately 5 days of infection. I am using this well defined model to study the mechanisms required for clearance of the pathogen. It is thought that the immune responses following the intestinal Salmonella infection might be involved in this process: Upon oral administration of Salmonella Typhimurium to mice, the bacterium penetrates the gastrointestinal epithelial barrier, and become ingested by professional antigen presenting cells which are able to stimulate the production of antibody producing cells. The development of specific white blood cells, so called cytotoxic T-cells, may also be involved.
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To study the mechanisms that are involved in clearance of bacteria at the end of the infection, I will be using mice with defects in the development of antibody producing cells and mice lacking specific elements of the innate immune system required for proper pathogen recognition. This will allow us to determine the impact of the innate and adaptive immune response to clear the pathogen at the end of an infection. The latter mechanisms are of interest for our basic research and may identify new strategies for disease prevention or vaccination.
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Kathrin Endt is a PhD student at the Institute of Microbiology of the ETH Zurich and member of the PhD program Microbiology and Immunology
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Author: Kathrin Endt |
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An Infections with Salmonella |
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View a film explaining the molecular mechanisms of an infection with Salmonella.
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Our research might help people in Africa |
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Martin Stupak works in the Institute of Plant Science at the ETH Zurich. For him it is important to work in applied research and he hopes that one day, people in Africa will benefit from the results of his research. Read the interview with Martin and find out what exactly he is trying to achieve and why he is doing his PhD in Zurich.
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Video clips with Erica Bogan |
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Erica Bogan grew up in Costa Rica and speaks Spanish fluently. In the interview, however, she answers effortlessly in German and English! Even though at the moment she spends 10 to 12 hours a day in the lab, she is not yet sure about her future in hard-core research. What other possibilities are there? See for yourself in the video clips with Erica.
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