Dai W J, Hemphill A, Waldvogel A, Ingold K, Deplazes P, Mossmann H, Gottstein B
Institute of Parasitology, University of Berne, CH-3001 Berne, Switzerland.
Infect Immun. 2001 Oct;69(10):6074-83. doi: 10.1128/IAI.69.10.6074-6083.2001.
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, TCRbeta(-/-), major histocompatibility complex class II (MHCII)(-/-)(CD4-deficient), and CD40(-/-) mice. The Em2(G11)-specific IgG synthesized in nude TCRbeta(-/-) 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 alphabeta+ 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.
多房棘球绦虫可引发泡型包虫病，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。增殖的寄生性绦虫蚴与宿主组织之间的物理屏障是无细胞的生发层（LL），其特征在于富含高分子量多糖成分。与富含蛋白质的粗制囊液抗原相反，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，通过向C57/BL6小鼠腹腔接种100个绦虫蚴囊泡进行常规感染后，持续生长的绦虫蚴及其抗原刺激在体内诱导了Th2偏移。同时，Th1细胞因子（白细胞介素-2和γ干扰素）的表达在慢性感染后期之前一直持续处于低水平。与重组蛋白II/3抗原相比，针对Em2（G11）抗原（包括所有IgG亚型）的特异性免疫球蛋白G（IgG）反应的亲和力一直保持在低水平。此外，Em2（G11）抗原在T细胞缺陷的无胸腺裸鼠、TCRβ（-/-）、主要组织相容性复合体II类（MHCII）（-/-）（CD4缺陷）和CD40（-/-）小鼠中诱导了特异性IgM和IgG反应。在裸鼠TCRβ（-/-）和MHCII（-/-）小鼠中合成的Em2（G11）特异性IgG主要为IgG3和IgG2a亚型，在CD40（-/-）小鼠中为IgG3和IgG2b亚型。这一发现表明，在体内，对多房棘球绦虫主要碳水化合物抗原Em2（G11）的IgG反应可以独立于αβ + CD4 + T细胞发生，且在没有CD40 - CD40配体相互作用的情况下发生；因此，无细胞LL的Em2（G11）抗原代表一种非T细胞依赖性抗原。在功能上，包裹性的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，并且由于其非T细胞依赖性的性质，通过调节宿主免疫反应发挥作用。
