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 alterna...

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Bibliographic Details
Published in:Parasite immunology 2008-06, Vol.30 (6-7), p.354-364
Main Authors: IRIGOÍN, F, LAICH, A, FERREIRA, A.M, FERNÁNDEZ, C, SIM, R.B, DÍAZ, A
Format: Article
Language:English
Subjects:
Animals
C1q
complement
Complement C1q - immunology
Complement C1q - metabolism
Complement C3b - immunology
Complement Factor B - antagonists & inhibitors
Complement Factor H - immunology
Complement Pathway, Alternative
Echinococcosis - immunology
Echinococcus
Echinococcus granulosus - immunology
factor B
Humans
inositol hexakisphosphate
Phytic Acid - immunology
Phytic Acid - metabolism
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Summary: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 (InsP₆), 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 InsP₆ 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, InsP₆ 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 InsP₆ 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.
ISSN:0141-9838
1365-3024
DOI:10.1111/j.1365-3024.2008.01034.x