Kraft Martin R, Klotz Christian, Bücker Roland, Schulzke Jörg-Dieter, Aebischer Toni
Unit 16 Mycotic and Parasitic Agents and Mycobacteria, Robert Koch-Institute, Berlin, Germany.
Institute of Clinical Physiology, Charité Campus Benjamin Franklin, Berlin, Germany.
Front Cell Infect Microbiol. 2017 Sep 26;7:421. doi: 10.3389/fcimb.2017.00421. eCollection 2017.
The protozoan parasite is responsible for more than 280 million cases of gastrointestinal complaints ("giardiasis") every year, worldwide. Infections are acquired orally, mostly via uptake of cysts in contaminated drinking water. After transformation into the trophozoite stage, parasites start to colonize the duodenum and upper jejunum where they attach to the intestinal epithelium and replicate vegetatively. Outcome of infections vary between individuals, from self-limiting to chronic, and asymptomatic to severely symptomatic infection, with unspecific gastrointestinal complaints. One proposed mechanism for pathogenesis is the breakdown of intestinal barrier function. This has been studied by analyzing trans-epithelial electric resistances (TEER) or by indicators of epithelial permeability using labeled sugar compounds in cell culture systems, mouse models or human biopsies and epidemiological studies. Here, we discuss the results obtained mainly with epithelial cell models to highlight contradictory findings. We relate published studies to our own findings that suggest a lack of barrier compromising activities of recent isolates of assemblage A, B, and E in a Caco-2 model system. We propose that this epithelial cell model be viewed as mimicking asymptomatic infection. This view will likely lead to a more informative use of the model if emphasis is shifted from aiming to identify virulence factors to defining non-parasite factors that arguably appear to be more decisive for disease.
这种原生动物寄生虫每年在全球导致超过2.8亿例胃肠道疾病（“贾第虫病”）。感染通过口服获得，主要是通过摄取受污染饮用水中的包囊。转化为滋养体阶段后，寄生虫开始在十二指肠和空肠上段定殖，它们附着在肠上皮并进行无性繁殖。感染的结果因人而异，从自限性到慢性，从无症状到症状严重，伴有非特异性胃肠道症状。一种提出的发病机制是肠屏障功能的破坏。这已通过分析跨上皮电阻（TEER）或使用细胞培养系统、小鼠模型或人类活检以及流行病学研究中的标记糖化合物作为上皮通透性指标来进行研究。在这里，我们讨论主要通过上皮细胞模型获得的结果，以突出相互矛盾的发现。我们将已发表的研究与我们自己的发现联系起来，我们的发现表明在Caco-2模型系统中，近期A、B和E组分离株缺乏破坏屏障的活性。我们建议将这种上皮细胞模型视为模拟无症状感染。如果将重点从旨在识别毒力因子转向确定对疾病似乎更具决定性的非寄生虫因子，这种观点可能会使该模型得到更有价值的应用。
