< i > Borrelia burgdorferi < /i > Induces TLR2-Mediated Migration of Activated Dendritic Cells in an < i > Ex Vivo < /i > Human Skin Model

by 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. 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 injectedB.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 toB.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 anex vivo human skin model to study DC-B.burgdorferi interactions. Using this model, we have demonstrated thatB.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 infect...
Source: PLoS One - Category: Biomedical Science Authors: Source Type: research