Impairment of Macrophage Presenting Ability and Viability by Echinococcus granulosus Antigens.
BACKGROUND
Despite advances toward an improved understanding of the evasive mechanisms leading to the establishment of cystic echinococcosis, the discovery of specific immunosuppressive mechanisms and related factors are of great interest in the development of an immunotherapeutic approach.


OBJECTIVE
To elucidate immunosuppressive effects of bioactive factors contained in chromatographic fractions from hydatid cystic fluid (HCF) of Echinococcus granulosus.


METHODS
Hydatid cystic fluid was fractionated by reverse phase chromatography. Non-specific Concanavalin A-driven proliferation of spleen cells was used to determine specific inhibitory fractions. Trypan blue exclusion test and flowcytometry analysis were performed to check whether highly inhibitory fractions of HCF have apoptotic effect on peritoneal macrophages. Western blot analysis was used to determine proteolytic effects of parasitic antigens on major histocompatibility complex (MHC) class II (I-a) contained in membrane proteins extract from macrophages.


RESULTS
High concentrations of HCF and few of chromatographic fractions suppressed spleen cells proliferation. Fractions 7 and 35 were the highest inhibitory fractions. Specifically fraction 35 and to a lesser extent HCF induced apoptosis in peritoneal naive macrophages. However, HCF and the fraction 7 proteolytically altered the expression of MHC class II molecules on peritoneal macrophages. The proteolytic molecule was identified to be a serine protease. Macrophages taken at the chronic and end phase from cystic echinococcosis-infected mice were able to uptake and process C-Ovalbumine-FITC. These cells expressed a drastically reduced level of (I-a) molecules.


CONCLUSIONS
Our study present new aspects of immune suppression function of E. granulosus. Further molecular characterization of apoptotic and proteolytic factors might be useful to develop immunotherapeutic procedure to break down their inhibitory effects.
Radiopharmaceutical Unit, National Centre of Sciences and Nuclear Technology, Sidi Thabet, Ariana, Tunisia.
Naceur
N
Mejri
Imed Eddine
IE
Hassen
Jenny
J
Knapp
Mouldi
M
Saidi
D000818:Animals; D017951:Antigen Presentation; D049109:Cell Proliferation; D056148:Chromatography, Reverse-Phase; D004443:Echinococcosis / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D048209:Echinococcus granulosus / Q000276:immunology*; D005260:Female; D006801:Humans; D057131:Immune Evasion; D007167:Immunotherapy; D008264:Macrophages / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology