borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity包柔氏螺旋体recurrentis雇佣了一个新颖的多功能表面蛋白与anti-complement anti-opsonic逃脱先天免疫和入侵潜力.pdfVIP

Borrelia recurrentis Employs a Novel Multifunctional Surface Protein with Anti-Complement, Anti-Opsonic and Invasive Potential to Escape Innate Immunity 1 1 1 2 3 4 Sonja Grosskinsky , Melanie Schott , Christiane Brenner , Sally J. Cutler , Peter Kraiczy , Peter F. Zipfel , 5 1 Markus M. Simon , Reinhard Wallich * 1 Infectious Immunology, Institute for Immunology, University of Heidelberg, Heidelberg, Germany, 2 School of Health and Bioscience, University of East London, Stratford, London, United Kingdom, 3 Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt/Main, Germany, 4 Department of Infection Biology, Leibniz-Institute for Natural Products Research, Jena, Germany, 5 Metschnikoff Laboratory, Max-Planck-Institute for Immunobiology, Freiburg, Germany Abstract Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrad