Relapsing fever spirochetes Borrelia recurrentis and B. duttonii acquire complement regulators C4b-binding protein and factor H.
Relapsing fever is a rapidly progressive and severe septic disease caused by certain Borrelia spirochetes. The disease is divided into two forms, i.e., epidemic relapsing fever, caused by Borrelia recurrentis and transmitted by lice, and the endemic form, caused by several Borrelia species, such as B. duttonii, and transmitted by soft-bodied ticks. The spirochetes enter the bloodstream by the vector bite and live persistently in plasma even after the development of specific antibodies. This leads to fever relapses and high mortality and clearly indicates that the Borrelia organisms utilize effective immune evasion strategies. In this study, we show that the epidemic relapsing fever pathogen B. recurrentis and an endemic relapsing fever pathogen, B. duttonii, are serum resistant, i.e., resistant to complement in vitro. They acquire the host alternative complement pathway regulator factor H on their surfaces in a similar way to that of the less serum-resistant Lyme disease pathogen, B. burgdorferi sensu stricto. More importantly, the relapsing fever spirochetes specifically bind host C4b-binding protein, a major regulator of the antibody-mediated classical complement pathway. Both complement regulators retained their functional activities when bound to the surfaces of the spirochetes. In conclusion, this is the first report of complement evasion by Borrelia recurrentis and B. duttonii and the first report showing capture of C4b-binding protein by spirochetes.
Meri
T
T
Haartman Institute, Department of Bacteriology and Immunology, P.O. Box 21, University of Helsinki, FIN-00014 Helsinki, Finland. taru.meri@helsinki.fi.
Cutler
S J
SJ
Blom
A M
AM
Meri
S
S
Jokiranta
T S
TS
D001898:Borrelia / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D025065:Borrelia burgdorferi / Q000276:immunology; D050716:Complement C4b-Binding Protein / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism*; D051056:Complement Inactivating Agents / Q000378:metabolism*; D006801:Humans; D012061:Relapsing Fever / Q000276:immunology / Q000378:metabolism*
D050716:Complement C4b-Binding Protein; D051056:Complement Inactivating Agents; D017242:Complement Factor H