Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA.
Infect Immun. 2012 Mar;80(3):968-74. doi: 10.1128/IAI.05421-11. Epub 2011 Dec 5.
Toxoplasma gondii is the causative agent of toxoplasmosis in human and animals. In a mouse model, T. gondii strains can be divided into three groups, including the virulent, intermediately virulent, and nonvirulent. The clonal type I, II, and III T. gondii strains belong to these three groups, respectively. To better understand the basis of virulence phenotypes, we investigated mouse gene expression responses to the infection of different T. gondii strains at day 5 after intraperitoneal inoculation with 500 tachyzoites. The transcriptomes of mouse peritoneal cells showed that 1,927, 1,573, and 1,009 transcripts were altered more than 2-fold by type I, II, and III infections, respectively, and that the majority of altered transcripts were shared. Overall transcription patterns were similar in type I and type II infections, and both had greater changes than infection with type III. Quantification of parasite burden in mouse spleens showed that the burden with type I infection was 1,000 times higher than that of type II and that the type II burden was 20 times higher than that of type III. Fluorescence-activated cell sorting revealed that type I and II infections had comparable macrophage populations, and both were higher than the population with type III infection. In addition, type I infection had a higher percentage of neutrophils than type II and III infections. Taken together, these results suggested that there is a common gene expression response to T. gondii infection in mice. This response is further modified by parasite strain-specific factors that determine their distinct virulence phenotypes.
刚地弓形虫是人类和动物弓形虫病的病原体。在小鼠模型中,刚地弓形虫株可分为三组,包括强毒、中度毒和无毒。克隆型 I、II 和 III 刚地弓形虫株分别属于这三组。为了更好地了解毒力表型的基础,我们研究了不同刚地弓形虫株感染小鼠后第 5 天腹膜细胞中基因表达的变化。腹膜细胞的转录组显示,I 型、II 型和 III 型感染分别使 1927、1573 和 1009 个转录物的表达改变了 2 倍以上,且大多数改变的转录物是共有的。I 型和 II 型感染的总体转录模式相似,且均比 III 型感染的变化更大。小鼠脾脏中的寄生虫负荷定量显示,I 型感染的负荷比 II 型高 1000 倍,而 II 型的负荷比 III 型高 20 倍。流式细胞术分析显示,I 型和 II 型感染的巨噬细胞群体相当,均高于 III 型感染的群体。此外,I 型感染的中性粒细胞比例高于 II 型和 III 型感染。综上所述,这些结果表明,小鼠对刚地弓形虫感染存在共同的基因表达反应。这种反应进一步受到寄生虫株特异性因素的修饰,这些因素决定了它们不同的毒力表型。