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 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.
Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Lauren M K
http://orcid.org/0000-0003-4944-3200
LM
Mason
Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Alex
A
Wagemakers
Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Cornelis
C
van 't Veer
Department of Medical Microbiology, Academic Medical Center, Amsterdam, the Netherlands.
Anneke
A
Oei
Department of Plastic Surgery, Kennemer Gasthuis, Haarlem, the Netherlands.
Wouter J
WJ
van der Pot
Department of Plastic Surgery, Kennemer Gasthuis, Haarlem, the Netherlands.
Kalam
K
Ahmed
Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.|Division of Infectious Diseases, Academic Medical Center, Amsterdam, the Netherlands.
Tom
T
van der Poll
Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands.
Teunis B H
TB
Geijtenbeek
Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.|Division of Infectious Diseases, Academic Medical Center, Amsterdam, the Netherlands.
Joppe W R
JW
Hovius
D015415:Biomarkers; D025065:Borrelia burgdorferi / Q000502:physiology*; D002465:Cell Movement / Q000276:immunology*; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008193:Lyme Disease / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
D015415:Biomarkers; D016207:Cytokines; D051195:Toll-Like Receptor 2
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