Complement evasion by Borrelia burgdorferi: serum-resistant strains promote C3b inactivation.
The most characteristic features of the Lyme disease pathogens, the Borrelia burgdorferi sensu lato (s.l.) group, are their ability to invade tissues and to circumvent the immune defenses of the host for extended periods of time, despite elevated levels of borrelia-specific antibodies in serum and other body fluids. Our aim in the present study was to determine whether B. burgdorferi is able to interfere with complement (C) at the level of C3 by accelerating C3b inactivation and thus to inhibit the amplification of the C cascade. Strains belonging to different genospecies (Borrelia garinii, B. burgdorferi sensu stricto, and Borrelia afzelii) were compared for their sensitivities to normal human serum and abilities to promote factor I-mediated C3b degradation. B. burgdorferi sensu stricto and B. afzelii strains were found to be serum resistant. When the spirochetes were incubated with radiolabeled C3b, factor I-mediated degradation of C3b was observed in the presence of C-resistant B. afzelii (n = 3) and B. burgdorferi sensu stricto (n = 1) strains but not in the presence of C-sensitive B. garinii (n = 7) strains or control bacteria (Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis). Immunoblotting and radioligand binding analyses showed that the C-resistant strains had the capacity to acquire the C inhibitors factor H and factor H-like protein 1 (FHL-1) from growth medium and human serum. A novel surface protein with an apparent molecular mass of 35 kDa was found to preferentially bind to the N terminus region of factor H. Thus, the serum-resistant B. burgdorferi s.l. strains can circumvent C attack by binding the C inhibitors factor H and FHL-1 to their surfaces and promoting factor I-mediated C3b degradation.
Alitalo
A
A
Department of Bacteriology and Immunology, Haartman Institute and HUCH Laboratory Diagnostics, FIN-00014 University of Helsinki, Finland.
Meri
T
T
Rämö
L
L
Jokiranta
T S
TS
Heikkilä
T
T
Seppälä
I J
IJ
Oksi
J
J
Viljanen
M
M
Meri
S
S
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000378:metabolism; D015748:Borrelia burgdorferi Group / Q000276:immunology* / Q000472:pathogenicity; D003167:Complement Activation / Q000276:immunology*; D003179:Complement C3b / Q000276:immunology*; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008193:Lyme Disease / Q000382:microbiology
D001426:Bacterial Proteins; D001798:Blood Proteins; C493495:CFH protein, human; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D003179:Complement C3b; D017242:Complement Factor H