Major carbohydrate antigen of Echinococcus multilocularis induces an immunoglobulin G response independent of alpha beta(+) CD4(+) T cells

Echinococcus multilocularis causes alveolar echinococcosis, one of the most lethal helminthic (accidental) infections in humans, as the life cycle pre dominantly includes wildlife rodents as intermediate hosts. The physical ba rrier between the proliferating parasitic metacestode and the host tissue i s the acellular laminated layer (LL), which is characterized by its rich hi gh-molecular-weight polysaccharide composition. Conversely to a crude prote in-rich vesicular fluid antigen, a major carbohydrate antigen of the LL-the Em2(G11) antigen-did not stimulate murine T-cell proliferation in vitro. I n fact, the persistent metacestode growth and antigenic stimulation induced a Th2 shift in vivo following conventional infection by intraperitoneal in oculation of 100 metacestode vesicles into C57/BL6 mice. Concurrently, the expression of Th1 cytokines (interleukin-2 and gamma interferon) remained p ersistently low until the late stage of chronic infection. In comparison to a recombinant proteinic II/3 antigen, the specific immunoglobulin G (IgG) response against the Em2(G11) antigen (including all IgG isotypes) maintain ed persistently low avidity. Furthermore, the Em2(G11) antigen induced a sp ecific IgM and IgG response in T-cell-deficient athymic nude, TCR beta (-/- ), major histocompatibility complex class II (MHCII)(-/-)(CD4-deficient), a nd CD40(-/-) mice. The Em2(G11)-specific IgG synthesized in nude TCR beta ( -/-) and MHCII-/- mice was predominantly of the IgG3 and IgG2a isotypes and of the IgG3 and IgG2b isotypes in CD40(-/-) mice. This finding suggested t hat in vivo, the IgG response to major carbohydrate antigen Em2(G11) of E. multilocularis could take place independently of alpha beta (+) CD4(+) T ce lls and in the absence of CD40-CD40 ligand interactions; thus, the Em2(G11) antigen of the acellular LL represents a T-cell-independent antigen. Funct ionally, the encapsulating LL, and especially its major carbohydrate antige n, Em2(G11), seems to be one of the key factors in the parasite's survival strategy and acts by modulating the host immune response by virtue of its T -cell-independent nature.