Immune evasion of Borrelia burgdorferi by acquisition of human complement regulators FHL-1/reconectin and Factor H.
To understand immune evasion mechanisms of Borrelia burgdorferi we compared serum-resistant B. afzelii and serum-sensitive B. garinii isolates for their capacity toacquire human complement regulators. Here we demonstrate that the two borrelial genospecies show different binding of the two important human complement regulators, FHL-1/reconectin and Factor H. All serum-resistant B. afzelii isolates bound FHL-1/reconectin and also Factor H, and all analyzed serum-sensitive B. garinii isolates showed no or a significantly lower binding activity. Using recombinant deletion mutants, the binding domains were localized to the C terminus of FHL-1/reconectin to short consensus repeats 5-7. The borrelial binding proteins were located in the surface of the bacteria as demonstrated by immunofluorescence staining of intact, serum-exposed bacteria and by enrichment of outer membrane proteins. The surface-attached complement regulators maintained complement regulatory activity as demonstrated in a cofactor assay. By ligand blotting two different borrelial binding proteins were identified that were responsible for the surface attachment of FHL-1/reconectin and Factor H. These borrelial complement regulators acquiring surface proteins (CRASP) were further characterized as either CRASP-1, a 27.5-kDa molecule which preferentially binds FHL-1/reconectin and which was present in all serum-resistant borreliae, or CRASP-2, a 20/21-kDa protein which interacts preferentially with Factor H and the expression of which was more restricted, being detected in four of the six isolates analyzed. In summary, we describe a new immune evasion mechanism of B. burgdorferi, as these bacteria acquire human complement regulators to control complement activation on their surface and to prevent formation of toxic activation products.
Kraiczy
P
P
Institute of Medical Microbiology, University Hospital of Frankfurt, Frankfurt, Germany.
Skerka
C
C
Kirschfink
M
M
Brade
V
V
Zipfel
P F
PF
D000327:Adsorption; D001426:Bacterial Proteins / Q000276:immunology; D001665:Binding Sites; D001798:Blood Proteins / Q000276:immunology*; D015748:Borrelia burgdorferi Group / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D003167:Complement Activation; D003179:Complement C3b / Q000276:immunology; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H / Q000276:immunology*; D006801:Humans; D008193:Lyme Disease / Q000382:microbiology / Q000473:pathology
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