Although several PFam54 members play an important role in the pathogenesis of Lyme disease, the exact function has been determined only for CspA, which binds complement regulator factor H (CFH) and factor H-like protein 1 (FHL-1); thus, CspA is essential to resist the vertebrate host's immune response.
Here, we use a natural rodent-Borrelia system to test for associations between landscape-level spatial variation in Borrelia infection risk along replicated elevational gradients in the Swiss Alps and Toll-like receptor 2 (TLR2) evolution, a candidate gene for Borrelia resistance, across bank vole (Myodes glareolus) populations.
The aim of the present study was to investigate the Arg753Gln single-nucleotide polymorphism (SNP) of the TLR2 gene, and the isoleucine to serine transversion at position 602 (Ile602Ser) of the TLR1 gene (previously associated with Lyme disease), in leptospirosis patients compared to healthy controls, carrying out a retrospective case/control study.
Phagocytosed Borrelia burgdorferi (Bb), the Lyme disease spirochete, induces a robust and complex innate immune response in human monocytes, in which TLR8 cooperates with TLR2 in the induction of NF-κB-mediated cytokine production, whereas TLR8 is solely responsible for transcription of IFN-β through IRF7.
The aim of this study was to select genes related to the alternative pathway of the complement system [including complement factor H (CFH)], differentiating the type of infection in the system model, that is, a culture of normal human diploid fibroblasts infected with three different spirochaete genospecies: Borrelia afzelii, Borrelia garinii and Borrelia burgdorferii sensu stricto, by comparing the infected fibroblast culture with the control fibroblast one.
Identification and characterization of the factor H and FHL-1 binding complement regulator-acquiring surface protein 1 of the Lyme disease spirochete Borrelia spielmanii sp. nov.
The goals of this study were to assess the ligand binding capability of CspZ orthologs derived from an extensive panel of human Lyme disease isolates and to further define the molecular basis of the interaction between FH and CspZ.
Systematic analysis highlights the key role of TLR2/NF-kappaB/MAP kinase signaling for IL-8 induction by macrophage-like THP-1 cells under influence of Borrelia burgdorferi lysates.
Dual binding specificity of a Borrelia hermsii-associated complement regulator-acquiring surface protein for factor H and plasminogen discloses a putative virulence factor of relapsing fever spirochetes.
Functional characterization of BbCRASP-2, a distinct outer membrane protein of Borrelia burgdorferi that binds host complement regulators factor H and FHL-1.
Increased TLR2 expression in unstimulated neutrophils suggests an important role of these cells in mechanism recognition of B burgdorferi in patients with Lyme disease.
Immunological and molecular analyses of the Borrelia hermsii factor H and factor H-like protein 1 binding protein, FhbA: demonstration of its utility as a diagnostic marker and epidemiological tool for tick-borne relapsing fever.
Evidence that the BBA68 protein (BbCRASP-1) of the Lyme disease spirochetes does not contribute to factor H-mediated immune evasion in humans and other animals.
In the present study we have elucidated the putative potential of other members of the gbb54 paralogous family, including orthologs ZSA66, ZSA69, ZSA70, ZSA71, ZSA72 and ZSA73 of the European B. burgdorferi s.s. strain ZS7, to bind human FHL-1 and factor H. In spite of their overall similarity in protein sequence, between 47% and 67%, and the fact that the C-terminal region of ZSA69 shows 70% similarity with BbCRASP-1, none of the orthologous proteins was able to bind human FHL-1 and/or factor H. BbCRASP-1 is the only member of the paralogous gene family gbb54 that binds to human complement regulators, supporting the notion that BbCRASP-1 plays a critical role in evasion of complement by B. burgdorferi s.s. and thus may be helpful in the development of novel therapeutic strategies against Lyme borreliosis.
Complement resistance of Borrelia burgdorferi correlates with the expression of BbCRASP-1, a novel linear plasmid-encoded surface protein that interacts with human factor H and FHL-1 and is unrelated to Erp proteins.
Complement inhibitor factor H binding to Lyme disease spirochetes is mediated by inducible expression of multiple plasmid-encoded outer surface protein E paralogs.
The toll-like receptor 2 (TLR2) has gained importance as a major mammalian receptor for lipoproteins derived from the cell wall of a variety of bacteria, such as Borrelia burgdorferi, Treponema pallidum, and Mycoplasma fermentans.