Taubert Anja, Zahner Horst, Hermosilla Carlos
Institute of Parasitology, Justus Liebig University Giessen, Giessen, Germany.
Vet Parasitol. 2006 Dec 20;142(3-4):214-22. doi: 10.1016/j.vetpar.2006.07.021. Epub 2006 Aug 22.
Sporozoites of Eimeria bovis and tachyzoites of Neospora caninum and Toxoplasma gondii are able to invade and to replicate in endothelial cells. Here we report on responses of bovine umbilical vein endothelial cells (BUVEC) in vitro to these coccidial infections by determining mRNA levels of the CXC chemokines GRO-alpha, IL-8 and IP-10, the CC chemokines MCP-1 and RANTES and of GM-CSF, COX-2 and iNOS relative to the level of housekeeping gene (GAPDH) transcription. T. gondii and N. caninum tachyzoites caused profound transcriptional upregulation of all genes in question. In general, upregulation started 2-4 h p.i. and maximum transcript levels were observed 4 h p.i. GRO-alpha and IL-8 gene transcription had decreased to almost control levels by 12 h p.i.; in the case of the other chemokines enhanced transcript levels persisted longer or showed a biphasic time-course. A similar time-course to CC chemokines was observed for GM-CSF mRNA, whilst COX-2 gene transcript peaks were detected at 2-4 h p.i. and 48-72 h p.i. iNOS mRNA levels increased from 4 to 48 h p.i. In contrast, E. bovis sporozoites failed to induce the transcription of CXC chemokine genes and of COX-2, and only caused moderate transcription upregulation of the other genes considered. In conclusion, infections of BUVEC with these coccidian parasites result in host cell activation associated with enhanced transcription of genes encoding for proinflammatory and immunomodulatory molecules, which are important for innate immune reactions and the transition to adaptive immunity. Differences between E. bovis versus T. gondii and N. caninum may illustrate a particular evasion strategy of E. bovis sporozoites, which is related to their need to persist in the host cell for a long period of time and to the avoidance of inflammatory process-induction.
牛艾美耳球虫的子孢子以及犬新孢子虫和刚地弓形虫的速殖子能够侵入内皮细胞并在其中复制。在此，我们通过测定CXC趋化因子GRO-α、IL-8和IP-10、CC趋化因子MCP-1和RANTES以及GM-CSF、COX-2和iNOS相对于管家基因（GAPDH）转录水平的mRNA水平，报告牛脐静脉内皮细胞（BUVEC）在体外对这些球虫感染的反应。刚地弓形虫和犬新孢子虫的速殖子导致所有相关基因的转录显著上调。一般来说，上调在感染后2-4小时开始，在感染后4小时观察到最大转录水平。GRO-α和IL-8基因转录在感染后12小时已降至几乎对照水平；对于其他趋化因子，增强的转录水平持续时间更长或呈现双相时间进程。GM-CSF mRNA观察到与CC趋化因子类似的时间进程，而COX-2基因转录峰值在感染后2-4小时和48-72小时检测到。iNOS mRNA水平在感染后4至48小时增加。相比之下，牛艾美耳球虫的子孢子未能诱导CXC趋化因子基因和COX-2的转录，仅导致所考虑的其他基因的适度转录上调。总之，这些球虫寄生虫感染BUVEC导致宿主细胞活化，与编码促炎和免疫调节分子的基因转录增强相关，这对于先天免疫反应和向适应性免疫的转变很重要。牛艾美耳球虫与刚地弓形虫和犬新孢子虫之间的差异可能说明了牛艾美耳球虫子孢子的一种特殊逃避策略，这与其在宿主细胞中长期存活的需要以及避免诱导炎症过程有关。
