Deng Mingqi, Lancto Cheryl A, Abrahamsen Mitchell S
Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, 1988 Fitch Avenue, St Paul, MN 55108, USA.
Int J Parasitol. 2004 Jan;34(1):73-82. doi: 10.1016/j.ijpara.2003.10.001.
Cryptosporidium parvum is an obligate intracellular protozoan capable of causing life-threatening diarrhoeal disease in immunocompromised individuals. Efforts to develop novel therapeutic strategies have been hampered by the lack of understanding of the pathogenesis of infection. To better understand the host response to C. parvum infection, gene expression profiles of infected human ileocecal adenocarcinoma cells were analysed by using Affymetrix oligonucleotide microarrays containing probe sets for 12,600 human genes. Statistical analysis of expression data from three independent experiments identified 223 genes whose expression was reproducibly regulated by C. parvum infection at 24 h post-inoculation (125 up-regulated and 98 down-regulated), 13 of which were validated by quantitative reverse transcriptase polymerase chain reaction analysis. This analysis revealed the consistent up-regulation of host heat-shock genes and genes for pro-inflammatory chemokines IL-8, RANTES, and SCYB5. Multiple genes for host actin and tubulin genes were up-regulated whereas genes for actin binding proteins were down-regulated, confirming previous observations of host cytoskeleton rearrangement in response to C. parvum infection. In addition, host genes associated with cell proliferation and apoptosis were differentially regulated, reflecting the complexity of host-parasite interaction. Together, this study demonstrated that C. parvum infection results in significant changes in host biochemical pathways and provides new insights into specific biological processes of infectious disease caused by an intracellular protozoan parasite.
微小隐孢子虫是一种专性细胞内原生动物，能够在免疫功能低下的个体中引起危及生命的腹泻疾病。由于对感染发病机制缺乏了解，开发新型治疗策略的努力受到了阻碍。为了更好地了解宿主对微小隐孢子虫感染的反应，利用包含12,600个人类基因探针集的Affymetrix寡核苷酸微阵列分析了受感染的人类回盲部腺癌细胞的基因表达谱。对来自三个独立实验的表达数据进行统计分析，确定了223个基因，其表达在接种后24小时可被微小隐孢子虫感染重复性调节（125个上调，98个下调），其中13个通过定量逆转录聚合酶链反应分析得到验证。该分析揭示了宿主热休克基因以及促炎趋化因子IL-8、RANTES和SCYB5基因的一致上调。多个宿主肌动蛋白和微管蛋白基因上调，而肌动蛋白结合蛋白基因下调，证实了先前关于宿主细胞骨架重排以响应微小隐孢子虫感染的观察结果。此外，与细胞增殖和凋亡相关的宿主基因受到差异调节，反映了宿主 - 寄生虫相互作用的复杂性。总之，这项研究表明微小隐孢子虫感染导致宿主生化途径发生显著变化，并为细胞内原生动物寄生虫引起的传染病的特定生物学过程提供了新的见解。
