Binding of the complement inhibitor C4b-binding protein to Lyme disease Borreliae.
The Lyme disease spirochetes, Borrelia burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii, are tick-borne pathogens that can cause chronic disseminated infections. To survive in the human host borreliae need to evade the immune system. It is already well known that B. burgdorferi ss. and B. afzelii bind the complement (C) alternative pathway inhibitor factor H from serum using OspE and CRASP-1/Bba68 proteins to escape C attack. In the presence of natural antibodies and in chronic infections, when specific antibodies develop, borreliae have to protect themselves from antibody-induced classical pathway C attack. In this study we demonstrate binding of the classical pathway inhibitor, C4b-binding protein (C4bp), to three genospecies of B. burgdorferi sensu lato. Binding was strongest to B. garinii, which has been found to be the weakest factor H binder. The bacteria bound both purified (125)I-labeled C4bp and C4bp from serum. Unlabeled C4bp competed for binding with (125)I-C4bp, whereas BSA had no effect. Binding was salt-sensitive and inhibited by C4b and partially by heparin. C4bp maintained its cofactor activity for factor I in cleaving C4b when bound to the bacterial surface. Ligand blotting analysis of whole cell lysates and fractionated outer cell membranes of the bacteria suggested one major receptor of approximately 43 kDa (P43) for C4bp in B. garinii and B. burgdorferi sensu stricto. Binding of C4bp may thus allow Lyme disease borreliae to escape activation of the classical C pathway and allow chronic infections in humans even in the presence of specific antibodies.
Pietikäinen
Johanna
J
Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, HUSLAB, Helsinki, Finland.
Meri
Taru
T
Blom
Anna M
AM
Meri
Seppo
S
D001898:Borrelia / Q000187:drug effects / Q000276:immunology*; D002457:Cell Extracts; D050716:Complement C4b-Binding Protein / Q000302:isolation & purification / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology*; D011485:Protein Binding / Q000187:drug effects; D011971:Receptors, Immunologic / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology
D002457:Cell Extracts; D050716:Complement C4b-Binding Protein; D008024:Ligands; D011971:Receptors, Immunologic; D012965:Sodium Chloride; D006493:Heparin