Onchocerca volvulus microfilariae avoid complement attack by direct binding of factor H.
The filarial parasite Onchocerca volvulus is the causative agent of river blindness. The adult worms produce microfilariae (mf), which are responsible for the disease pathogenesis; mf activate the complement system, but the activation stops before the formation of terminal complement complexes. Because of the arrest of complement activation, this study analyzed binding of the main alternative pathway regulator, factor H (fH), to the mf. The mf bound fH after incubation in nonimmune human serum or with purified radiolabeled fH. In the presence of factor I, mf-bound fH promoted the cleavage of complement 3 molecule b (C3b) to iC3b. An analysis with recombinant constructs of fH showed that the C-terminal short consensus repeats (SCRs) 8-20 of fH bound to mf, whereas the N-terminal SCRs 1-7 containing the complement-regulatory domains in SCRs 1-5 did not. Thus, mf of the nematode O. volvulus may evade human complement by binding fH and by promoting inactivation of C3b into iC3b.
Meri
Taru
T
Department of Bacteriology and Immunology, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, FIN-00014 Helsinki, Finland. Taru.Meri@helsinki.fi
Jokiranta
T Sakari
TS
Hellwage
Jens
J
Bialonski
Alexandra
A
Zipfel
Peter F
PF
Meri
Seppo
S
D000818:Animals; D003167:Complement Activation / Q000276:immunology; D003179:Complement C3b / Q000276:immunology; D017242:Complement Factor H / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008842:Microfilariae / Q000276:immunology*; D008856:Microscopy, Fluorescence; D017181:Onchocerca volvulus / Q000276:immunology*; D011485:Protein Binding
C493495:CFH protein, human; D003179:Complement C3b; D017242:Complement Factor H; D003165:Complement System Proteins