Borrelia burgdorferi Induces TLR2-Mediated Migration of Activated Dendritic Cells in an Ex Vivo Human Skin Model.
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 lymp...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5047638?pdf=render |
| _version_ | 1819106909428383744 |
|---|---|
| author | Lauren M K Mason Alex Wagemakers Cornelis van 't Veer Anneke Oei Wouter J van der Pot Kalam Ahmed Tom van der Poll Teunis B H Geijtenbeek Joppe W R Hovius |
| author_facet | Lauren M K Mason Alex Wagemakers Cornelis van 't Veer Anneke Oei Wouter J van der Pot Kalam Ahmed Tom van der Poll Teunis B H Geijtenbeek Joppe W R Hovius |
| author_sort | Lauren M K Mason |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T02:45:38Z |
| format | Article |
| id | doaj.art-62509e432cb74b9b806e6f5f7eb51c46 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T02:45:38Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-62509e432cb74b9b806e6f5f7eb51c462022-12-21T18:41:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011110e016404010.1371/journal.pone.0164040Borrelia burgdorferi Induces TLR2-Mediated Migration of Activated Dendritic Cells in an Ex Vivo Human Skin Model.Lauren M K MasonAlex WagemakersCornelis van 't VeerAnneke OeiWouter J van der PotKalam AhmedTom van der PollTeunis B H GeijtenbeekJoppe W R HoviusBorrelia 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.http://europepmc.org/articles/PMC5047638?pdf=render |
| spellingShingle | Lauren M K Mason Alex Wagemakers Cornelis van 't Veer Anneke Oei Wouter J van der Pot Kalam Ahmed Tom van der Poll Teunis B H Geijtenbeek Joppe W R Hovius Borrelia burgdorferi Induces TLR2-Mediated Migration of Activated Dendritic Cells in an Ex Vivo Human Skin Model. PLoS ONE |
| title | Borrelia burgdorferi Induces TLR2-Mediated Migration of Activated Dendritic Cells in an Ex Vivo Human Skin Model. |
| title_full | Borrelia burgdorferi Induces TLR2-Mediated Migration of Activated Dendritic Cells in an Ex Vivo Human Skin Model. |
| title_fullStr | Borrelia burgdorferi Induces TLR2-Mediated Migration of Activated Dendritic Cells in an Ex Vivo Human Skin Model. |
| title_full_unstemmed | Borrelia burgdorferi Induces TLR2-Mediated Migration of Activated Dendritic Cells in an Ex Vivo Human Skin Model. |
| title_short | Borrelia burgdorferi Induces TLR2-Mediated Migration of Activated Dendritic Cells in an Ex Vivo Human Skin Model. |
| title_sort | borrelia burgdorferi induces tlr2 mediated migration of activated dendritic cells in an ex vivo human skin model |
| url | http://europepmc.org/articles/PMC5047638?pdf=render |
| work_keys_str_mv | AT laurenmkmason borreliaburgdorferiinducestlr2mediatedmigrationofactivateddendriticcellsinanexvivohumanskinmodel AT alexwagemakers borreliaburgdorferiinducestlr2mediatedmigrationofactivateddendriticcellsinanexvivohumanskinmodel AT cornelisvantveer borreliaburgdorferiinducestlr2mediatedmigrationofactivateddendriticcellsinanexvivohumanskinmodel AT annekeoei borreliaburgdorferiinducestlr2mediatedmigrationofactivateddendriticcellsinanexvivohumanskinmodel AT wouterjvanderpot borreliaburgdorferiinducestlr2mediatedmigrationofactivateddendriticcellsinanexvivohumanskinmodel AT kalamahmed borreliaburgdorferiinducestlr2mediatedmigrationofactivateddendriticcellsinanexvivohumanskinmodel AT tomvanderpoll borreliaburgdorferiinducestlr2mediatedmigrationofactivateddendriticcellsinanexvivohumanskinmodel AT teunisbhgeijtenbeek borreliaburgdorferiinducestlr2mediatedmigrationofactivateddendriticcellsinanexvivohumanskinmodel AT joppewrhovius borreliaburgdorferiinducestlr2mediatedmigrationofactivateddendriticcellsinanexvivohumanskinmodel |