Major carbohydrate antigen of Echinococcus multilocularis induces an immunoglobulin G response independent of αβ+ CD4+ T cells

被引:72
作者
Dai, WJ
Hemphill, A
Waldvogel, A
Ingold, K
Deplazes, P
Mossmann, H
Gottstein, B
机构
[1] Univ Bern, Inst Parasitol, CH-3001 Bern, Switzerland
[2] Univ Bern, Inst Anim Pathol, CH-3001 Bern, Switzerland
[3] Univ Zurich, Inst Parasitol, CH-8057 Zurich, Switzerland
[4] Max Planck Inst Immunbiol, D-7800 Freiburg, Germany
关键词
D O I
10.1128/IAI.69.10.6074-6083.2001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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, TCR beta (-/-), major histocompatibility complex class II (MHCII)(-/-)(CD4-deficient), and 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 that in vivo, the IgG response to major carbohydrate antigen Em2(G11) of E. multilocularis could take place independently of alpha beta (+) 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.
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页码:6074 / 6083
页数:10
相关论文
共 53 条
  • [1] Functional diversity of helper T lymphocytes
    Abbas, AK
    Murphy, KM
    Sher, A
    [J]. NATURE, 1996, 383 (6603) : 787 - 793
  • [2] Secondary alveolar echinococcosis in lymphotoxin-α and tumour necrosis factor-α deficient mice:: exacerbation of Echinococcus multilocularis larval growth is associated with cellular changes in the periparasitic granuloma
    Amiot, F
    Vuong, P
    Defontaines, M
    Pater, C
    Dautry, F
    Liance, M
    [J]. PARASITE IMMUNOLOGY, 1999, 21 (09) : 475 - 483
  • [3] EFFECT OF CHEMOTHERAPY ON THE LARVAL MASS AND THE LONG-TERM COURSE OF ALVEOLAR ECHINOCOCCOSIS
    AMMANN, RW
    ILITSCH, N
    MARINCEK, B
    FREIBURGHAUS, AU
    [J]. HEPATOLOGY, 1994, 19 (03) : 735 - 742
  • [4] The role of germinal centers for antiviral B cell responses
    Bachmann, MF
    [J]. IMMUNOLOGIC RESEARCH, 1998, 17 (03) : 329 - 344
  • [5] Bachmann MF, 1998, J IMMUNOL, V161, P5791
  • [6] Neutralizing antiviral B cell responses
    Bachmann, MF
    Zinkernagel, RM
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 : 235 - 270
  • [7] Antibody response in CD4-depleted mice after immunization or during early infection with Echinococcus granulosus
    Baz, A
    Richieri, A
    Puglia, A
    Nieto, A
    Dematteis, S
    [J]. PARASITE IMMUNOLOGY, 1999, 21 (03) : 141 - 150
  • [8] BRESSONHADNI S, 1990, CLIN EXP IMMUNOL, V82, P378, DOI 10.1111/j.1365-2249.1990.tb05457.x
  • [9] Buchanan RM, 1998, J IMMUNOL, V161, P5525
  • [10] Dai WJ, 1999, IMMUNOLOGY, V97, P107, DOI 10.1046/j.1365-2567.1999.00723.x