Lau A O, Sacci J B, Azad A F
Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
J Immunol. 2001 Feb 1;166(3):1945-50. doi: 10.4049/jimmunol.166.3.1945.
The liver stage of malaria, caused by the genus Plasmodium, is clinically silent, but immunologically significant. Ample evidence exists for an effective CD8(+) T cell response to this stage as well as the involvement of gammadeltaT cells and NK1.1(int) cells in immunized animal models. In contrast, there is little information concerning responses in a naive host. Here we report that several host gene expressions in the liver, spleen, and kidney of BALB/c mice are altered during the liver stage of Plasmodium yoelii infection. Really interesting new gene 3 (Ring3), semaphorin subclass 4 member G, glutamylcysteine synthetase, and p45 NF erythroid 2 were all up-regulated 24 h after infection with P. yoelii. Semaphorin subclass 4 member G expression was elevated in the kidney, whereas Ring3 was elevated in both spleen and kidney. The expression of TNF-alpha (TNF-alpha and IFN-gamma) were down-regulated in all three tissues tested except in infected spleen where IFN-gamma was elevated. P. yoelii-related host gene changes were compared with those in Toxoplasma gondii-infected livers. Ring3 expression increased 5-fold over control values, whereas expression of the other transcripts remained unchanged. TNF-alpha and IFN-gamma expressions were increased in the Toxoplasma-infected livers. The uniform increase of Ring3 expression in both Plasmodium- and Toxoplasma-infected livers suggests an innate immune response against parasitic infections, whereas the other gene expression changes are consistent with Plasmodium parasite-specific responses. Taken together, these changes suggest the immune responses to P. yoelii infection are both parasite and organ specific.
由疟原虫属引起的疟疾肝期在临床上没有症状，但在免疫方面具有重要意义。有充分证据表明，针对这一阶段存在有效的CD8(+) T细胞反应，以及γδT细胞和NK1.1(int)细胞在免疫动物模型中的参与。相比之下，关于未感染宿主的反应的信息很少。在此我们报告，在约氏疟原虫感染的肝期，BALB/c小鼠肝脏、脾脏和肾脏中的几种宿主基因表达发生了改变。感染约氏疟原虫24小时后，真有趣新基因3（Ring3）、信号素亚类4成员G、谷氨酰半胱氨酸合成酶和p45 NF红细胞2均上调。信号素亚类4成员G在肾脏中表达升高，而Ring3在脾脏和肾脏中均升高。除感染的脾脏中IFN-γ升高外，在所有测试的三个组织中，TNF-α（TNF-α和IFN-γ）的表达均下调。将约氏疟原虫相关的宿主基因变化与弓形虫感染的肝脏中的变化进行了比较。Ring3的表达比对照值增加了5倍，而其他转录本的表达保持不变。在弓形虫感染的肝脏中，TNF-α和IFN-γ的表达增加。在疟原虫和弓形虫感染的肝脏中Ring3表达的一致增加表明对寄生虫感染的先天免疫反应，而其他基因表达变化与疟原虫寄生虫特异性反应一致。综上所述，这些变化表明对约氏疟原虫感染的免疫反应既是寄生虫特异性的，也是器官特异性的。
