GIARDIAL CROSSTALK WITH THE HUMAN INTESTINAL EPITHELIUM

蓝氏贾第鞭毛虫是世界范围内引起疟疾的主要原因， 其发病机制知之甚少。滋养体不是 已知入侵，表达任何毒力因子，或引发炎症 反应因此，了解心血管相互作用至关重要 寄生虫和宿主的肠上皮细胞 perspective.该单位的总体目标是阐明分子， 细胞和生物化学之间的串扰， 体外和人肠中的人肠上皮细胞 异种移植模型潜在的假设是生理刺激 可以调节心血管行为， 滋养体更好地殖民和逃避自然宿主防御。 相反，滋养体的附着可能引起生理上相关的 对宿主上皮屏障的反应。我们将决定是否 串扰是由于心包膜附着于活细胞或由 释放到环境中的因素。目的一是研究滋养体 生存。，生长和附着反应培养的人肠 上皮细胞目的2是检验暴露于 上皮细胞或来自它们的信号可以：A.导致包囊滋养体 从分化恢复到生长; B.改变整个滋养体 通过蛋白质、蛋白质和蛋白质水平的改变 磷酸化和mRNA指纹; C.诱导表达Giardiac 毒力因子目的3是检验依恋将 引起两种滋养体细胞骨架和超微结构的变化 和肠上皮细胞，这可能会提供关键的见解， 交互.目的4是评价人异种肠移植模型， 一个研究正常肠上皮细胞对 胃肠道定植。该系统将允许我们定义主机和 感染所需的寄生虫因素。 这些研究将大大扩展我们对一个重要的 肠道寄生虫，并有可能产生新的见解， 肠屏障和防御功能。

Giardia lamblia is a major cause of diarrheal disease worldwide, yet little is known of its mechanisms of pathogenesis. Trophozoites are not known to invade, express any virulence factor, or elicit an inflammatory response. Therefore, it is crucial to understand giardial interactions with the intestinal epithelium from both the parasite and the host perspective. The overall goal of this Unit is to elucidate the molecular, cellular, and biochemical cross talk between giardial trophozoites and human intestinal epithelial cells in vitro and in a human intestinal xenograft model. The underlying hypothesis is that physiologic stimuli from host epithelial cells may modulate giardial behavior and enable trophozoites to better colonize and evade natural host defenses. Conversely, attachment of trophozoites may elicit physiologically relevant responses to the host epithelial barrier. We will determine whether the cross talk is due to giardial attachment to live cells or caused by factors released into the environment. Aim 1 is to investigate trophozoite survival., growth, and attachment responses to cultured human intestinal epithelial cells. Aim 2 is to test the hypothesis that exposure to epithelial cells or signals from them may: A. cause encysting trophozoites to revert from differentiation to growth; B. change overall trophozoite development programs as manifested by alterations in protein, protein phosphorylation, and mRNA fingerprints; C. induce expression of giardial virulence factors. Aim 3 is to test the hypothesis that attachment will induce changes in the cytoskeleton and ultrastructure of both trophozoites and intestinal epithelial cells that may give key insights into their interactions. Aim 4 is to evaluate the human intestinal xenograft model as a system to study the response of normal intestinal epithelial cells to giardial colonization. This system will allow us to define both host and parasite factors required for infection. These studies will greatly extend our understanding of an important intestinal parasite and have the potential to yield new insights into intestinal barrier and defense functions.