Resistance of the Echinococcus granulosus cyst wall to complement activation: analysis of the role of InsP6 deposits.
The larva of the cestode Echinococcus granulosus (hydatid cyst) is protected by the acellular laminated layer (LL). The mechanisms that make this thick coat a poor activator of host complement are incompletely understood. The structure binds, through unknown motifs, the host regulator of the alternative complement pathway (ACP), factor H. A second potential mechanism of ACP regulation, the inhibition of factor B activation, was detected in assays employing purified components (Immunopharmacology 42 : 91). The inhibitor was subsequently identified as myo-inositol hexakisphosphate (InsP(6)), which in the form of nano-deposits is a major component of the LL (Biochem J 362 : 297; J Cell Biochem 93 : 1272; FEBS J 273 : 3192). In this report we show that colloidal InsP(6 )solids inhibit factor B activation, through adsorption and associated impairment of C3b binding. However, this interaction is not relevant in the presence of serum proteins. In serum, InsP(6) deposits instead bind C1q, and initiate complement activation. This activation is curtailed through efficient C3b inactivation, previously shown to be entirely factor H-dependent, and now observed to be independent of the InsP(6) deposits. Therefore the complement resistance of the LL must be based on functional factor H binding sites present on the mucin-based meshwork that is its other major constituent.
Irigoín
F
F
Department of Biosciences, Immunology Laboratory, Faculty of Chemistry, Institute for Biological Chemistry, Faculty of Sciences, University of the Republic, Montevideo, Uruguay.
Laich
A
A
Ferreira
A M
AM
Fernández
C
C
Sim
R B
RB
Díaz
A
A
D000818:Animals; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism; D003179:Complement C3b / Q000276:immunology; D011415:Complement Factor B / Q000037:antagonists & inhibitors; D017242:Complement Factor H / Q000276:immunology; D003170:Complement Pathway, Alternative; D004443:Echinococcosis / Q000276:immunology*; D048209:Echinococcus granulosus / Q000276:immunology*; D006801:Humans; D010833:Phytic Acid / Q000276:immunology* / Q000378:metabolism
D010833:Phytic Acid; D015922:Complement C1q; D003179:Complement C3b; D017242:Complement Factor H; D011415:Complement Factor B