Modulation of Human Immune Response byEchinococcus granulosusAntigen B and Its Possible Role in Evading Host Defenses

Abstract

). AgB skewed the Th1/Th2 cytokine ratios towards a preferentially immunopathology-associated Th2 polarization, predominantly in patients with progressive disease. AgB-stimulated patients' PBMC also proliferated less than SHF-stimulated PBMC (P ‫؍‬ 9 ؋ 10 ؊3 ). In vitro Th2 cytokine production was reflected in vivo by elevated specific immunoglobulin E (IgE) and IgG4 antibodies binding to AgB. These findings confirm that AgB plays a role in the escape from early immunity by inhibiting PMN chemotaxis. They also add new information on the host-parasite relationship, suggesting that AgB exploits the activation of T helper cells by eliciting a nonprotective Th2 cell response.Cystic echinococcosis (CE) is a widely endemic helminthic disease caused by infection with metacestodes (larval stage) of the tapeworm Echinococcus granulosus. It affects humans and a wide range of livestock species (28). The disease is characterized by the growth in the host internal organs, mostly liver and lungs, of steadily growing fluid-filled, unilocular cysts surrounded by a two-layered hydatid cyst wall. The main feature of the host-parasite relationship is the coexistence of the chronic infection with detectable humoral and cellular responses against the parasite. Parasite survival in vivo depends on efficient evasion mechanisms starting to operate as the parasite develops toward a hydatid cyst. A fibrotic host capsule of variable thickness usually develops, thus forming together with the parasite-derived acellular laminated layer a formidable cystic structure. As a consequence, the actively dividing germinal layer within the cyst along with its associated brood capsule and enclosed protoscoleces are effectively sequestered from the host immune responses. In addition to this physical barrier, the hydatid cyst has probably evolved other strategies for immune evasion. Although older models suggested a more passive role for parasites in immune evasion-for example sequestration, antigenic masking by host proteins, and global immunosuppression-later studies suggest in human parasitoses the active deployment of strategies that manipulate and exploit the host response (12, 30).

Contingent, non-neutral evolution in a multicellular parasite: natural selection and gene conversion in the Echinococcus granulosus antigen B gene family

“…About 10% of the hydatid fluid protein fraction is composed by a polymeric thermo-stable lipoprotein (Musiani et al, 1978), the antigen B (AgB), whose role in the immune response evasion is suggested by several lines of evidence. First, the antigen inhibits neutrophil chemotaxis and elastases in vitro (Shepherd et al, 1991); second, it elicits a non-protective Th2 immune response (Riganú et al, 2001); and, finally, it induces immune cell apopoptosis in patients with hydatid disease (Riganú et al, 2002). The native antigen, built by subunits of 8 kDa, is highly immunoreactive.…”

Identification of Critical Residues of an Immunodominant Region of Echinococcus granulosus Antigen B

“…The antigen is present in large amounts in the metacestode cyst fluid, and its biological functions suggest that it may play a relevant role in the host/parasite interaction. AgB has been reported as a protease inhibitor that impairs the recruitment of polymorphonuclear cells and skews the Th1/Th2 cytokine ratio toward an immunopathology-associated Th2 polarization (4,5). In human infections, AgB is highly immunogenic, which has prompted its use as a diagnostic reagent.…”

Efficiency Evaluation of Immunization Protocol with Echinococcus Granulosus Antigen B (Agb)

“…Most studies on CE cytokines are mainly based on in vitro experiments, determination of cytokine production following stimulation of peripheral blood mononuclear cell or T helper cells of patients and healthy with crude and B antigens [20,6]. These studies demonstrated an increasing in the production of some cytokines such as IFN-γ, IL-4, and IL-5.…”

“…AgB can be measured in patient blood as circulating antigen [4], and it has been suggested that it plays an important role in the biology of the parasite and its relationship with the host [5,6].AgB is a highly immunogenic molecule, a characteristic that underpins its value in serodiagnosis . It appears ladder-like under reduced condition on SDS-PAGE, with three bands with molecular sizes of approximately 8 or 12, 16, and 24 kDa, suggesting that it comprises polymers of 8-kDa subunits [7].The smallest subunit has proved the most useful target in diagnostic studies [8].Observing that the 12-kDa subunit of AgB is a protease inhibitor with the ability to inhibit neutrophil recruitment.…”