Borrelia burgdorferi clinical isolates induce human innate immune responses that are not dependent on genotype

Mason, Lauren M.K.; Herkes, Eduard A.; Krupna-Gaylord, Michelle A.; Oei, Arlene L.; Poll, Tom van der; Wormser, Gary P.; Schwartz, Ira; Petzke, Mary M.; Hovius, Joppe W.

doi:10.1016/j.imbio.2015.06.006

Cited by 14 publications

(9 citation statements)

References 38 publications

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“…Although there is a range of inflammatory potential for a given Borrelia RST strain ( 31 ), we previously showed in vivo and in vitro that B. burgdorferi from the northeastern United States induced greater inflammatory responses than B. afzelii and B. garinii from Europe ( 4 , 8 ). In this study, we demonstrated in cell culture that B. burgdorferi from Europe and the United States vary in inflammatory potential.…”

Section: Discussionmentioning

confidence: 99%

Differences in Genotype, Clinical Features, and Inflammatory Potentialof Borrelia burgdorferisensu stricto Strains from Europe and the United States

Cerar¹,

Strle²,

Stupica³

et al. 2016

Emerg. Infect. Dis.

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Section: Discussionmentioning

confidence: 99%

Differences in Genotype, Clinical Features, and Inflammatory Potentialof Borrelia burgdorferisensu stricto Strains from Europe and the United States

Cerar¹,

Strle²,

Stupica³

et al. 2016

Emerg. Infect. Dis.

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“…MoDCs were generated from adherent monocytes isolated from the blood of healthy volunteers by density gradient using Ficoll paque (GE-healthcare, Uppsala, Sweden) and Percoll (GE-healthcare) and cultured in Roswell Park Memorial Institute (RPMI) 1640 medium (Gibco, Paisley, UK) with 10% FCS and L-glutamine supplemented with 1000 U/ml interleukin (IL)-4 (Prospec, East Brunswick, NJ, USA) and 50 ng/ml Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) (Gibco) at 37°C with 5% CO 2 , as previously described [ 11 ]. A total of 1 x 10 5 moDCs in RPMI medium with 10% FCS and L-glutamine were stimulated for 48 hours with different multiplicities of infection of B .…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2016

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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.

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“…Non‐reservoir mammalian hosts (e.g. humans or M. musculus mouse models) in vivo , cultivated macrophages, or dendritic cells in vitro develop distinct levels of cytokines and chemokines in response to different Lyme borreliae species/strains (Strle et al , ; ; Mason et al , ). The ability to trigger varying degrees of cytokine and chemokine production in different species/strains during infection is strongly correlated with the severity of resulting manifestations (Widhe et al , ; Jones et al , ; Strle et al , ; ).…”

Section: Hosts Develop Variable Levels Of Innate and Adaptive Immune mentioning

confidence: 99%

Outer surface protein polymorphisms linked to host‐spirochete association in Lyme borreliae

Tufts

Hart

Chen

et al. 2019

Molecular Microbiology

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Summary Lyme borreliosis is caused by multiple species of the spirochete bacteria Borrelia burgdorferi sensu lato. The spirochetes are transmitted by ticks to vertebrate hosts including small and mediumsized mammals, birds, reptiles, and humans. Strain-to-strain variation in host specific infectivity has been documented, but the molecular basis that drives this differentiation is still unclear. Spirochetes possess the ability to evade host immune responses and colonize host tissues to establish infection in vertebrate hosts. In turn, hosts have developed distinct levels of immune responses when invaded by different species/strains of Lyme borreliae. Similarly, the ability of Lyme borreliae to colonize host tissues varies among different spirochete species/strains. One potential mechanism that drives this strain-to-strain variation of immune evasion and colonization is the polymorphic outer surface proteins produced by Lyme borreliae. In this review, we summarize research on strain-to-strain variation in host competence and discuss the evidence that supports the role of spirocheteproduced protein polymorphisms in driving this variation in host specialization. Such information will provide greater insights into the adaptive mechanisms driving host and Lyme borreliae association, which will lead to the development of interventions to block pathogen spread and eventually reduce Lyme borreliosis health burden.

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Borrelia burgdorferi clinical isolates induce human innate immune responses that are not dependent on genotype

Cited by 14 publications

References 38 publications

Differences in Genotype, Clinical Features, and Inflammatory Potentialof Borrelia burgdorferisensu stricto Strains from Europe and the United States

Differences in Genotype, Clinical Features, and Inflammatory Potentialof Borrelia burgdorferisensu stricto Strains from Europe and the United States

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

Outer surface protein polymorphisms linked to host‐spirochete association in Lyme borreliae

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