Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity.
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 degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever.
Grosskinsky
Sonja
S
Infectious Immunology, Institute for Immunology, University of Heidelberg, Heidelberg, Germany.
Schott
Melanie
M
Brenner
Christiane
C
Cutler
Sally J
SJ
Kraiczy
Peter
P
Zipfel
Peter F
PF
Simon
Markus M
MM
Wallich
Reinhard
R
D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D001898:Borrelia / Q000276:immunology* / Q000472:pathogenicity*; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism*; D003165:Complement System Proteins; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D009895:Opsonin Proteins; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding
D001426:Bacterial Proteins; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D009895:Opsonin Proteins; D017242:Complement Factor H; D010958:Plasminogen; D003165:Complement System Proteins