Affiliation:
1. Institute of Parasitology1 and
2. Institute of Animal Pathology,2 University of Berne, CH-3001 Berne, and
3. Institute of Parasitology, University of Zurich, Zurich,3 Switzerland, and
4. Max Plank Institute for Immunobiology, Freiburg, Germany4
Abstract
ABSTRACT
Echinococcus multilocularis
causes alveolar echinococcosis, one of the most lethal helminthic (accidental) infections in humans, as the life cycle predominantly includes wildlife rodents as intermediate hosts. The physical barrier between the proliferating parasitic metacestode and the host tissue is the acellular laminated layer (LL), which is characterized by its rich high-molecular-weight polysaccharide composition. Conversely to a crude protein-rich vesicular fluid antigen, a major carbohydrate antigen of the LL—the Em2(G11) antigen—did not stimulate murine T-cell proliferation in vitro. In fact, the persistent metacestode growth and antigenic stimulation induced a Th2 shift in vivo following conventional infection by intraperitoneal inoculation of 100 metacestode vesicles into C57/BL6 mice. Concurrently, the expression of Th1 cytokines (interleukin-2 and gamma interferon) remained persistently 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) maintained persistently low avidity. Furthermore, the Em2(G11) antigen induced a specific IgM and IgG response in T-cell-deficient athymic nude, TCRβ
−/−
, major histocompatibility complex class II (MHCII)
−/−
(CD4-deficient), and CD40
−/−
mice. The Em2(G11)-specific IgG synthesized in nude TCRβ
−/−
and MHCII
−/−
mice was predominantly of the IgG3 and IgG2a isotypes and of the IgG3 and IgG2b isotypes in CD40
−/−
mice. This finding suggested that in vivo, the IgG response to major carbohydrate antigen Em2(G11) of
E. multilocularis
could take place independently of αβ
+
CD4
+
T cells and in the absence of CD40-CD40 ligand interactions; thus, the Em2(G11) antigen of the acellular LL represents a T-cell-independent antigen. Functionally, the encapsulating LL, and especially its major carbohydrate antigen, 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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
77 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献