Modulation of human immune response by Echinococcus granulosus antigen B and its possible role in evading host defenses

By directly suppressing the function of certain immune cell subsets and by stimulating other cell populations related to immunopathology, parasite-der ived substances play an important role in the chronic establishment of para sitic disease. Our objective was twofold: (i) to investigate further the ro le of Echinococcus granulosus antigen B (AgB) in the human early inflammato ry response by determining its effect on polymorphonuclear cell (PMN) rando m migration, chemotaxis, and oxidative metabolism and (ii) to determine its action in acquired immunity by evaluating AgB and sheep hydatid fluid (SHF )-driven Th1 (gamma interferon [IFN-gamma] and interleukin 12 [IL-12]) and Th2 (IL-4 and IL-13) cytokine production by peripheral blood mononuclear ce lls (PBMC) from 40 patients who had cured or stable or progressive cystic e chinococcosis. AgB significantly inhibited PMN recruitment but left their r andom migration and oxidative metabolism unchanged. Patients' PBMC stimulat ed with AgB produced IL-4 and IL-13 but did not produce IL-12. They also pr oduced significantly lower IFN-gamma concentrations than did PBMC stimulate d with SHF (P = 10(-5)). AgB skewed the Th1/Th2 cytokine ratios towards a p referentially immunopathology-associated Th2 polarization, predominantly in patients with progressive disease. AgB-stimulated patients' PBMC also prol iferated less than SHF-stimulated PBMC (P = 9 x 10(-3)). In vitro Th2 cytok ine production was reflected in vivo by elevated specific immunoglobulin E (IgE) and IgG4 antibodies binding to AgB. These findings confirm that AgB p lays a role in the escape from early immunity by inhibiting PMN chemotaxis. They also add new information on the host-parasite relationship, suggestin g that AgB exploits the activation of T helper cells by eliciting a nonprot ective Th2 cell response.