1. Inadequate binding of immune regulator factor H is associated with sensitivity of Borrelia lusitaniae to human complement.
- Author
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Dieterich R, Hammerschmidt C, Richter D, Skerka C, Wallich R, Matuschka FR, Zipfel PF, and Kraiczy P
- Subjects
- Animals, Bacterial Outer Membrane Proteins chemistry, Bacterial Outer Membrane Proteins genetics, Bacterial Outer Membrane Proteins metabolism, Blood Bactericidal Activity, Blood Proteins, Borrelia classification, Borrelia genetics, Borrelia isolation & purification, Borrelia Infections microbiology, Complement C3b Inactivator Proteins, Complement Factor H chemistry, Germany, Humans, Ixodes microbiology, Molecular Sequence Data, Portugal, Sequence Analysis, DNA, Borrelia metabolism, Borrelia Infections immunology, Complement Activation immunology, Complement Factor H metabolism, Complement Pathway, Alternative immunology
- Abstract
Spirochetes belonging to the Borrelia burgdorferi sensu lato complex differ in resistance to complement-mediated killing by human serum. Here, we characterize complement sensitivity of a panel of B. lusitaniae isolates derived from ticks collected in Germany and Portugal as well as one patient-derived isolate, PoHL. All isolates are highly susceptible to complement-mediated lysis in human serum and activate complement predominantly by the alternative pathway, leading to an increased deposition of complement components C3, C6, and the terminal complement complex. Interestingly, serum-sensitive B. lusitaniae isolates were able to bind immune regulator factor H (CFH), and some strains also bound CFH-related protein 1 (CFHR1) and CFHR2. Moreover, CFH bound to the surface of B. lusitaniae was inefficient in mediating C3b conversion. Furthermore, the identification and characterization of a potential CFH-binding protein, OspE, revealed that this molecule possesses a significantly reduced binding capacity for CFH compared to that of CFH-binding OspE paralogs expressed by various serum-resistant Borrelia species. This finding suggests that a reduced binding capability of CFH is associated with an increased serum sensitivity of B. lusitaniae to human complement.
- Published
- 2010
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