Major carbohydrate antigen of Echinococcus multilocularis induces an immunoglobulin G response independent of αβ+ CD4+ T cells
Major carbohydrate antigen of Echinococcus multilocularis induces an immunoglobulin G response independent of αβ+ CD4+ T cells
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DOI：
10.1128/iai.69.10.6074-6083.2001
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发表时间：
2001-10-01
影响因子：
3.1
通讯作者：
Gottstein, B
中科院分区：
文献类型：
--
作者：
Dai, WJ;Hemphill, A;Gottstein, B
多房棘球绦虫引起肺泡包虫病，这是人类最致命的蠕虫（意外）感染之一，因为其生命周期主要包括野生啮齿动物作为中间宿主。增殖的寄生后绦虫与宿主组织之间的物理屏障是无细胞层压层（LL），其特征在于其丰富的高分子量多糖成分。与富含粗蛋白的囊泡液抗原相反，LL 的主要碳水化合物抗原——Em2(G11) 抗原——在体外不会刺激小鼠 T 细胞增殖。事实上，通过将 100 个后绦虫囊泡腹膜内接种到 C57/BL6 小鼠中进行常规感染后，持续的后绦虫生长和抗原刺激诱导了体内 Th2 转变。同时，Th1细胞因子（白细胞介素2和γ干扰素）的表达持续较低，直到慢性感染晚期。与重组蛋白 II/3 抗原相比，针对 Em2(G11) 抗原（包括所有 IgG 同种型）的特异性免疫球蛋白 G (IgG) 反应始终保持较低的亲和力。此外，Em2(G11) 抗原在 T 细胞缺陷的无胸腺裸鼠、TCR beta (-/-)、主要组织相容性复合物 II 类 (MHCII)(-/-)（CD4 缺陷）和 CD40(-/-) 小鼠中诱导特异性 IgM 和 IgG 反应。在裸TCRβ(-/-)和MHCII-/-小鼠中合成的Em2(G11)特异性IgG主要是IgG3和IgG2a同种型，在CD40(-/-)小鼠中主要是IgG3和IgG2b同种型。这一发现表明，在体内，在不存在 CD40-CD40 配体相互作用的情况下，多房艾美耳球虫对主要碳水化合物抗原 Em2(G11) 的 IgG 反应可以独立于 alpha beta (+) CD4(+) T 细胞发生。因此，非细胞 LL 的 Em2(G11) 抗原代表 T 细胞非依赖性抗原。从功能上讲，封装的 LL，尤其是其主要碳水化合物抗原 Em2(G11)，似乎是寄生虫生存策略的关键因素之一，并凭借其不依赖于 T 细胞的性质通过调节宿主免疫反应来发挥作用。
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.