Vuitton Dominique Angèle
'Health and Rural Environnement' Research Unit (EA 2276), University Laboratory of Immunology, Université de Franche-Comté and University Hospital, F-25030, Besançon, France.
Acta Trop. 2003 Feb;85(2):119-32. doi: 10.1016/s0001-706x(02)00230-9.
In Echinococcus infection, at the metacestode stage, studies of the immune responses in the experimental murine model as well as in humans have shown that (1) cellular immunity induced by a Th1-type cytokine secretion was able to successfully kill the metacestode at the initial stages of development; (2) antigenic proteins and carbohydrates (and perhaps non-antigenic, mitogenic components) of the oncosphere/metacestode were able to interfere with antigen presentation and cell activation so that host lymphocytes and other immune cells could produce cytokines (especially IL-10) and other mediators able to inhibit the effector phase of cellular immune reaction; and (3) immunogenetic characteristics of the host were essential to this parasite-induced deviation of the immune response. In E. multilocularis infection, a combined Th1 and Th2 cytokine profile appears crucial for prolonged metacestode growth and survival. It may be hypothesized that Th1 cytokines promote the initial cell recruitment around the metacestode and are involved in the chronicity of the cell infiltrate leading to a fully organized periparasitic granuloma and its consequences, fibrosis and necrosis. The Th2 cytokines, on the other hand, could be responsible for the inhibition of a successful parasite killing especially because of the 'anti-inflammatory' potency of IL-10. This combination of various arms of the immune response results in a partial protection of both Echinococcus metacestode and host. However, it may also be considered responsible for several complications of the disease. The Th2-related IgE synthesis and mast cell activation, well known to be responsible for anaphylactic reactions in cystic echinococcosis, are more rarely involved in 'allergic' complications in alveolar echinococcosis (AE). However, the partial but chronic effects of the efficient Th1-related cellular immune response are responsible for cytotoxic events which both help metacestode growth and dissemination and lead to the central necrosis of the lesions and clinical complications of AE. Moreover, the Th-1 response is responsible for the major and irreversible fibrosis which leads to bile duct and vessel obstruction. In addition, the peri-parasitic fibrosis may be one of the reasons for the relative lack of efficacy of antiparasitic drugs. Modulation of the host immune response, by using Interferon alpha for instance, may be a new tool to generate an effective immune response against the parasite and to prevent AE and its complications.
在棘球蚴感染的成虫期，对实验鼠模型以及人类免疫反应的研究表明：（1）由Th1型细胞因子分泌诱导的细胞免疫能够在发育初期成功杀死成虫；（2）六钩蚴/成虫的抗原性蛋白质和碳水化合物（或许还有非抗原性的促有丝分裂成分）能够干扰抗原呈递和细胞激活，从而使宿主淋巴细胞和其他免疫细胞能够产生细胞因子（尤其是IL-10）以及其他能够抑制细胞免疫反应效应阶段的介质；（3）宿主的免疫遗传特征对于这种寄生虫诱导的免疫反应偏差至关重要。在多房棘球绦虫感染中，Th1和Th2细胞因子的联合特征对于成虫的长期生长和存活似乎至关重要。可以推测，Th1细胞因子促进成虫周围的初始细胞募集，并参与细胞浸润的慢性过程，导致形成完全组织化的寄生虫周围肉芽肿及其后果，即纤维化和坏死。另一方面，Th2细胞因子可能是抑制成功杀死寄生虫的原因，特别是因为IL-10具有“抗炎”作用。免疫反应各方面的这种组合导致棘球蚴成虫和宿主都得到部分保护。然而，这也可能是该疾病几种并发症的原因。众所周知，与Th2相关的IgE合成和肥大细胞激活是囊性棘球蚴病过敏反应的原因，在肺泡棘球蚴病（AE）的“过敏”并发症中较少涉及。然而，有效的Th1相关细胞免疫反应的部分但慢性影响是细胞毒性事件的原因，这些事件既有助于成虫的生长和传播，又导致病变的中央坏死和AE的临床并发症。此外，Th-1反应是导致主要且不可逆纤维化的原因，进而导致胆管和血管阻塞。此外，寄生虫周围纤维化可能是抗寄生虫药物疗效相对不足的原因之一。例如，通过使用α干扰素调节宿主免疫反应，可能是产生针对寄生虫的有效免疫反应并预防AE及其并发症的新工具。
