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Published on: May 19, 2023
Borrelia miyamotoi Activates Human Dendritic Cells and Elicits T Cell Responses
Lauren M K Mason1, Joris Koetsveld2, Jos J A Trentelman2
1Center for Experimental and Molecular Medicine, Amsterdam Infection and Immunity, Amsterdam University Medical Center, University of Amsterdam, 1105AZ Amsterdam, the Netherlands; l.m.mason@amc.uva.nl.
Abstract:
The spirochete Borrelia miyamotoi has recently been shown to cause relapsing fever. Like the Lyme disease agent, Borrelia burgdorferi, B. miyamotoi is transmitted through the bite of infected ticks; however, little is known about the response of the immune system upon infection. Dendritic cells (DCs) play a central role in the early immune response against B. burgdorferi We investigated the response of DCs to two different strains of B. miyamotoi using in vitro and ex vivo models and compared this to the response elicited by B. burgdorferi. Our findings show that B. miyamotoi is phagocytosed by monocyte-derived DCs, causing upregulation of activation markers and production of proinflammatory cytokines in a similar manner to B. burgdorferi. Recognition of B. miyamotoi was demonstrated to be partially mediated by TLR2. DCs migrated out of human skin explants upon inoculation of the skin with B. miyamotoi. Finally, we showed that B. miyamotoi-stimulated DCs induced proliferation of naive CD4+ and CD8+ T cells to a larger extent than B. burgdorferi. In conclusion, we show in this study that DCs respond to and mount an immune response against B. miyamotoi that is similar to the response to B. burgdorferi and is able to induce T cell proliferation.
Insights
Borrelia miyamotoi infection triggers dendritic cell (DC) activation and cytokine production, similar to Borrelia burgdorferi. DCs stimulated by B. miyamotoi also induce greater T cell proliferation.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Borrelia miyamotoi causes relapsing fever and is tick-borne, like the Lyme disease agent Borrelia burgdorferi.
- The immune system's response to B. miyamotoi infection is not well understood.
- Dendritic cells (DCs) are crucial for early immune responses against Borrelia species.
Purpose of the Study:
- To investigate the response of dendritic cells (DCs) to Borrelia miyamotoi.
- To compare the DC response to B. miyamotoi with that elicited by Borrelia burgdorferi.
- To understand the role of DCs in the immune response to B. miyamotoi infection.
Main Methods:
- In vitro and ex vivo models using human monocyte-derived DCs and skin explants.
- Analysis of DC activation markers, cytokine production, and migration.
- Comparison of DC responses to B. miyamotoi and B. burgdorferi.
- Assessment of T cell proliferation induced by B. miyamotoi-stimulated DCs.
Main Results:
- B. miyamotoi was phagocytosed by DCs, leading to activation marker upregulation and pro-inflammatory cytokine production, similar to B. burgdorferi.
- Toll-like receptor 2 (TLR2) partially mediated the recognition of B. miyamotoi.
- DCs migrated from human skin explants upon B. miyamotoi inoculation.
- B. miyamotoi-stimulated DCs induced greater proliferation of CD4+ and CD8+ T cells compared to B. burgdorferi.
Conclusions:
- Dendritic cells mount an immune response to B. miyamotoi that is comparable to the response against B. burgdorferi.
- The immune response involves DC activation, cytokine production, migration, and induction of T cell proliferation.
- These findings highlight the role of DCs in controlling B. miyamotoi infections.
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