title: Migration of Salmonella typhimurium --harboring bone marrow--derived dendritic cells towards the chemokines CCL19 and CCL21.
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.
authors.affiliation: Institut für Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Cédric
authors.initials: C
authors.lastname: Cheminay
authors.forename: Matthias
authors.initials: M
authors.lastname: Schoen
authors.forename: Michael
authors.initials: M
authors.lastname: Hensel
authors.forename: Alexandra
authors.initials: A
authors.lastname: Wandersee-Steinhäuser
authors.forename: Uwe
authors.initials: U
authors.lastname: Ritter
authors.forename: Heinrich
authors.initials: H
authors.lastname: Körner
authors.forename: Martin
authors.initials: M
authors.lastname: Röllinghoff
authors.forename: Joachim
authors.initials: J
authors.lastname: Hein
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000382:microbiology*; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000276:immunology*; D002633:Chemotaxis; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012313:RNA / Q000737:chemistry / Q000235:genetics; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000254:growth & development / Q000276:immunology*
chemical_list: C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D012313:RNA