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Migration of Salmonella typhimurium --harboring bone marrow--derived dendritic cells towards the chemokines CCL19 and CCL21
Authors:Cheminay Cédric  Schoen Matthias  Hensel Michael  Wandersee-Steinhäuser Alexandra  Ritter Uwe  Körner Heinrich  Röllinghoff Martin  Hein Joachim
Institution:1. Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany;2. Nachwuchsgruppe 1 of the Interdisziplinäre Zentrum für Klinische Forschung (IZKF) at the Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany;1. First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan;2. Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan;3. Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan;1. The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, PR China;2. Bioinspired Engineering and Biomechanics Center (BEBC), Xi’an Jiaotong University, Xi’an 710049, PR China;1. The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, PR China;2. Bioinspired Engineering and Biomechanics Center (BEBC), Xi’an Jiaotong University, Xi’an 710049, PR China;3. From the Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115;4. Centenary Institute, National Health and Medical Research Council Clinical Trials Centre, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia;5. Department of Medicine/Rheumatology, Washington University School of Medicine, St. Louis, Missouri 63110;1. College of Life Science, Hebei Normal University, NO. 20 Road East of 2nd Ring South, Shijiazhuang, Hebei 050024, People’s Republic of China;2. College of Environmental Science and Engineering, Hebei University of Science and Technology, Shijiazhuang, Hebei 050018, People’s Republic of China
Abstract:Macrophages are considered as main cellular target encountered by the facultative intracellular bacterium Salmonella typhimurium. However, in orally infected mice these pathogens are first internalized by dendritic cells (DCs) that are located in the subepithelial dome of Peyer's patches. Moreover, DCs can penetrate the intestinal epithelium to sample bacteria. Here, we examined the interaction of Salmonella with bone marrow-derived DCs (BM-DCs). In order to study the role of DCs as vehicles for the dissemination of Salmonella, an in vitro model was established. In this model, Salmonella -activated BM-DCs enhanced surface expression of MHC class II and co-stimulatory molecules. We found that, upon maturation, BM-DCs upregulated chemokine receptor 7 (CCR7) mRNA and surface molecule expression. Salmonella -exposed DCs as well as mature DCs, but not immature DCs, were recruited towards the CC chemokines CCL19 and CCL21, two ligands of CCR7. The maturation process of DCs did neither require bacterial internalization nor viability. About one third of the migrated BM-DCs harbored intracellular bacteria, whereas the remaining two third did not contain bacteria. Salmonella, but not an apathogenic E. coli laboratory strain was capable to survive within BM-DCs. Taken together, our data implicate that DCs are first activated and subsequently utilized as carriers by Salmonella.
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