为了赢得对抗寄生虫病的斗争，必须了解发病机理的分子细节。最近的三项研究确定了所涉及的贾第鞭毛虫分泌的蛋白质。强调了感染过程中毒力因素的重要性及其作为新药物靶标的潜力。

贾迪亚and giardiasis

300年前，当安东尼·范·李温（Antony van Leeuwenhoek）凝视着他自己的腹泻凳子时，他的单镜显微镜凝视着他的腹泻凳子时，他受到了一位笑脸的游泳者的欢迎，正如他迷人地描述的那样： -“I have sometimes also seen tiny creatures moving very prettily; some of them a bit bigger, others a bit less, than a blood-globule but all of one and the same make. Their bodies were somewhat longer than broad, and their belly, which was flattish, furnished with sundry little paws, wherewith they made such a stir in the clear medium and among the globules, that you might even fancy you saw a woodlouse running up against a wall; and albeit they made a quick motion with their paws, yet for all that they made but slow progress.”

贾第虫属传播通过囊肿的摄入from contaminated water or raw food and is responsible for over 280 million symptomatic cases of parasitic diarrhoea worldwide every year. After passing through the stomach, trophozoites emerge in the small intestine and colonise its upper part. Trophozoites are responsible for giardiasis, which can take the form of a watery diarrhoea – explosive and foul-smelling. However, clinical manifestations are highly variable ranging from acute to chronic infections with many, perhaps most infections remaining entirely asymptomatic. The established narrative of pathogenesis is trophozoite attachment to the duodenal epithelium via a ventral disc which sometimes (but not always) causes villus atrophication by apoptosis (programmed cell death) of surrounding cells, initiating inflammation and disrupting intestinal barrier function. With integral roles for parasite secreted intermediates such as proteases in the degradation of intracellular junctions having been described.

Secreted virulence factors contribute to Giardia pathogenesis

贾迪亚are single-celled eukaryotes diverging from the main eukaryotic tree close to its root and, consequently, divergent to ours in many aspects of cell biology. The endomembrane system of Giardia is peculiar in many respects, perhaps most notably the golgi apparatus is conspicuous by its absence. Considerable work has been done to investigate endocytosis. Two key sets of secretory vesicles have been identified and roles for the endoplasmic reticulum have been proposed. However, when it comes to steady state secretion by the trophozoite form little is known for certain.

Features such as“裸露的斑块”，这是腹盘的液泡结构，被推测是类似于锥虫鞭毛口袋的动态膜运输的场所。这可能在宿主细胞附着期间发生，并且有人提出，某些毒力因子的附着，上调和分泌后可能发生，并有助于某些患者在十二指肠中观察到的局部损害和炎症。

局部损害并不是造成严重腹泻的唯一原因，它可能会影响消化道的肠道吸收，而不是定植的部位，这表明可溶性，分泌的，毒力因素的作用。

检查参与组成分泌腺的术语用来表示所有的秒reted proteins in the extracellular space. These secreted proteins can be identified and quantified through mass spectrometry-based proteomics platforms. Three recent research articles萨曼莎·埃默里（Samantha Emery）及其同事发表在科学报告中，，，，PLOS忽略了Showgy Ma’yaeh及其同事的热带疾病在奥黛丽·杜布格（Audrey Dubourg）并且同事们已经培训了蛋白质组学和生物信息学技术传达的能力，这些技术是关于贾第鞭gro滋养的问题的问题，分泌的蛋白质是否为贾第鞭毛虫谱系，环境如何调节分泌以及分泌产品如何影响肠道上皮。

Secretomes and infection

When Samantha Emery and colleagues addressed the secreted factors and mechanisms behind the origin of the infective cycle of attachment; they were able to show that trophozoites respond independently to host soluble signals early in pathogenesis, and that initial exposure to these secretions prompts a switch to a motile population phenotype. Conversely, Showgy Ma’ayeh and collaborators focused on identifying up-regulated secreted virulence factors from Giardia and evaluating their effects on the intestinal epithelia. They highlighted the importance of both host and parasite secreted proteins during the infection and the intricate and localized cellular responses occurring during a cognate interaction. Where the other two articles explored the effects of Giardia secretion upon interactions with the intestinal epithelia with which they were interacting, Audrey Dubourg and her colleagues produced a high resolution profile of the concentration of proteins being secreted by trophozoites grown in the absence of intestinal epithelia, to pinpoint the proteins secreted independently of colonisation or interaction with the host cells. They showed that Giardia trophozoites secrete only a very select group of proteins, but that these are secreted at quite high concentrations and are sufficient to disable the normal function of enteric epithelial cells even at very high dilution.

贾第鞭毛虫发病机理的新模型结合了分泌组

Most of the proteins highlighted as secreted and up-regulated by trophozoites belong to three major group of proteins: Giardia tenascins, cathepsin B precursors (GCATBs) and high cysteine membrane proteins (HCMPs). Trophozoites also release other proteins with specific roles associated with niche adaptation.
From these studies, a novel mechanism of early pathogenesis has been proposed:

1.吡二胺5'5'5'5'5'PONPO（PNPO），由贾第烷分泌，产生一个减少的环境，有利于贾第鞭毛虫的滋养体生长
2.贾第鞭毛外细胞核酸酶降解肠粘膜的外层，赋予更好地进入粘液层进入GCATBS
3. Further degradation of the protective intestinal mucus barrier may be caused by GCATBs as well as subsequent disruption of the intestinal intracellular junctions
4. Tenistin可能负责减少上皮细胞之间的粘附，从而维持肠细胞分离。这是通过在肠上皮细胞表面存在的表皮生长因子（EGF）受体的连接来实现的。上皮完整性的这种丧失潜在地驱动的损失增加了更多独立的肠细胞中的凋亡，并立即导致上皮的吸收和屏障功能失调。
5. Giardia mediated dismantling of the barriers provided by the mucosal membranes and modulation of the environment leaves the intestinal epithelia prone to secondary infections by opportunist microbes residing in the intestinal lumen and sensitive to irritation by allergens in foodstuffs. Secondary infections likely contributing to further inflammation and to the characteristic symptoms of giardiasis.