Müller N, von Allmen N
Institute of Parasitology, Länggass-Str. 122, CH-3012 Bern, Switzerland.
Int J Parasitol. 2005 Nov;35(13):1339-47. doi: 10.1016/j.ijpara.2005.07.008. Epub 2005 Aug 24.
Giardia lamblia is an intestinal protozoan parasite infecting humans and various other mammalian hosts. The most important clinical signs of giardiasis are diarrhoea and malabsorption. Giardia lamblia is able to undergo continuous antigenic variation of its major surface antigen, named VSP (variant surface protein). While intestinal antibodies, and more specifically anti-VSP IgA antibodies, were proven to be involved in modulating antigenic variation of the parasite the participation of the local antibody response in control of the parasite infection is still controversial. Conversely, previous studies based on experimental infections in mice showed that cellular immune mechanisms are essential for elimination of the parasite from its intestinal habitat. Furthermore, recent data indicated that inflammatory mast cells have a potential to directly, or indirectly, interfere in duodenal growth of G. lamblia trophozoites. However, this finding was challenged by other reports, which did not find a correlation between intestinal inflammation and resistance to infection. Since intestinal infiltration of inflammatory cells and/or CD8+T-cells were demonstrated to coincide with villus-shortening and crypt hyperplasia immunological reactions were considered to be a potential factor of pathogenesis in giardiasis. The contribution of physiological factors to pathogenesis was essentially assessed in vitro by co-cultivation of G. lamblia trophozoites with epithelial cell lines. By using this in vitro model, molecular (through surface lectins) and mechanical (through ventral disk) adhesion of trophozoites to the epithelium was shown to be crucial for increased epithelial permeability. This phenomenon as well as other Giardia-induced intestinal abnormalities such as loss of intestinal brush border surface area, villus flattening, inhibition of disaccharidase activities, and eventually also overgrowth of the enteric bacterial flora seem to be involved in the pathophysiology of giardiasis. However, it remains to be elucidated whether at least part of these pathological effects are causatively linked to the clinical manifestation of the disease.
蓝氏贾第鞭毛虫是一种感染人类和其他多种哺乳动物宿主的肠道原生动物寄生虫。贾第虫病最重要的临床症状是腹泻和吸收不良。蓝氏贾第鞭毛虫能够对其主要表面抗原，即变异表面蛋白（VSP）进行持续的抗原变异。虽然肠道抗体，更具体地说是抗VSP IgA抗体，已被证明参与调节寄生虫的抗原变异，但局部抗体反应在控制寄生虫感染中的作用仍存在争议。相反，先前基于小鼠实验感染的研究表明，细胞免疫机制对于从肠道栖息地清除寄生虫至关重要。此外，最近的数据表明，炎性肥大细胞有可能直接或间接干扰蓝氏贾第鞭毛虫滋养体在十二指肠的生长。然而，这一发现受到了其他报告的质疑，这些报告未发现肠道炎症与抗感染能力之间存在相关性。由于已证明炎性细胞和/或CD8 + T细胞的肠道浸润与绒毛缩短和隐窝增生同时出现，免疫反应被认为是贾第虫病发病机制的一个潜在因素。生理因素对发病机制的贡献主要通过将蓝氏贾第鞭毛虫滋养体与上皮细胞系共培养在体外进行评估。通过使用这种体外模型，已表明滋养体通过分子（通过表面凝集素）和机械（通过腹吸盘）方式与上皮细胞粘附对于增加上皮通透性至关重要。这种现象以及其他由贾第虫引起的肠道异常，如肠道刷状缘表面积丧失、绒毛扁平化、双糖酶活性抑制，最终还有肠道细菌菌群过度生长，似乎都参与了贾第虫病的病理生理学过程。然而，这些病理效应中至少有一部分是否与疾病的临床表现存在因果关系仍有待阐明。
