Borrelia burgdorferi Induces TLR2-Mediated Migration of Activated Dendritic Cells in an Ex Vivo Human Skin Model
Autor: | Teunis B.H. Geijtenbeek, Tom van der Poll, Alex Wagemakers, Cornelis van 't Veer, Wouter J. van der Pot, Anneke Oei, Joppe W. Hovius, Lauren M.K. Mason, Kalam Ahmed |
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Přispěvatelé: | Other departments, Center of Experimental and Molecular Medicine, Infectious diseases, Experimental Immunology |
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Physiology Biopsy lcsh:Medicine Human skin Pathology and Laboratory Medicine 0302 clinical medicine Spectrum Analysis Techniques Cell Movement Immune Physiology Medicine and Health Sciences lcsh:Science Routes of Administration Skin Lyme Disease Innate Immune System Multidisciplinary biology Spirochetes integumentary system Pattern recognition receptor Cell migration hemic and immune systems Flow Cytometry Bacterial Pathogens Cell Motility Medical Microbiology Spectrophotometry Cytokines Cytophotometry Pathogens Anatomy Integumentary System Research Article Borrelia Burgdorferi Cell Survival Immunology Surgical and Invasive Medical Procedures chemical and pharmacologic phenomena Cell Migration Research and Analysis Methods Microbiology 03 medical and health sciences Immune system Intradermal Injections Humans Borrelia burgdorferi Microbial Pathogens Pharmacology Bacteria Borrelia lcsh:R Organisms Biology and Life Sciences Dendritic cell Dendritic Cells Cell Biology Molecular Development biology.organism_classification Toll-Like Receptor 2 TLR2 030104 developmental biology Immune System lcsh:Q Ex vivo Biomarkers 030215 immunology Developmental Biology |
Zdroj: | PLoS ONE, 11(10). Public Library of Science PLoS ONE PLoS ONE, Vol 11, Iss 10, p e0164040 (2016) |
Popis: | Borrelia burgdorferi is transmitted into the skin of the host where it encounters and interacts with two dendritic cell (DC) subsets; Langerhans cells (LCs) and dermal DCs (DDCs). These cells recognize pathogens via pattern recognition receptors, mature and migrate out of the skin into draining lymph nodes, where they orchestrate adaptive immune responses. In order to investigate the response of skin DCs during the early immunopathogenesis of Lyme borreliosis, we injected B. burgdorferi intradermally into full-thickness human skin and studied the migration of DCs out of the skin, the activation profile and phenotype of migrated cells. We found a significant increase in the migration of LCs and DDCs in response to B. burgdorferi. Notably, migration was prevented by blocking TLR2. DCs migrated from skin inoculated with higher numbers of spirochetes expressed significantly higher levels of CD83 and produced pro-inflammatory cytokines. No difference was observed in the expression of HLA-DR, CD86, CD38, or CCR7. To conclude, we have established an ex vivo human skin model to study DC-B. burgdorferi interactions. Using this model, we have demonstrated that B. burgdorferi-induced DC migration is mediated by TLR2. Our findings underscore the utility of this model as a valuable tool to study immunity to spirochetal infections. |
Databáze: | OpenAIRE |
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