PDF(Pubmed)
Abstract：
UNASSIGNED: Toxoplasma gondii is an intracellular parasite of importance to human and veterinary health. The structure and diversity of the genotype population of T. gondii varies considerably with respect to geography, but three lineages, type I, II and III, are distributed globally. Lineage III genotypes are the least well characterized in terms of biology, host immunity and virulence. Once a host is infected with T.gondii, innate immune mechanisms are engaged to reduce the parasite burden in tissues and create a pro-inflammatory environment in which the TH1 response develops to ensure survival. This study investigated the early cellular immune response of Swiss-Webster mice post intraperitoneal infection with 10 tachyzoites of four distinct non-clonal genotypes of lineage III and a local isolate of ToxoDB#1. The virulence phenotype, cumulative mortality (CM) and allele profiles of ROP5, ROP16, ROP18 and GRA15 were published previously.
UNASSIGNED: Parasite dissemination in different tissues was analyzed by real-time PCR and relative expression levels of IFNγ, IL12-p40, IL-10 and TBX21 in the cervical lymph nodes (CLN), brain and spleen were calculated using the ΔΔCt method. Stage conversion was determined by detection of the BAG1 transcript in the brain.
UNASSIGNED: Tissue dissemination depends on the virulence phenotype but not CM, while the TBX21 and cytokine levels and kinetics correlate better with CM than virulence phenotype. The earliest detection of BAG1 was seven days post infection. Only infection with the genotype of high CM (69.4%) was associated with high T-bet levels in the CLN 24 h and high systemic IFNγ expression which was sustained over the first week, while infection with genotypes of lower CM (38.8%, 10.7% and 6.8%) is characterized by down-regulation and/or low systemic levels of IFNγ. The response intensity, as assessed by cytokine levels, to the genotype of high CM wanes over time, while it increases gradually to genotypes of lower CM.
UNASSIGNED: The results point to the conclusion that the immune response is not correlated with the virulence phenotype and/or allele profile, but an early onset, intense pro-inflammatory response is characteristic of genotypes with high CM. Additionally, high IFNγ level in the brain may hamper stage conversion.
UNASSIGNED: Parasite dissemination in different tissues was analyzed by real-time PCR and relative expression levels of IFNγ, IL12-p40, IL-10 and TBX21 in the cervical lymph nodes (CLN), brain and spleen were calculated using the ΔΔCt method. Stage conversion was determined by detection of the BAG1 transcript in the brain.
UNASSIGNED: Tissue dissemination depends on the virulence phenotype but not CM, while the TBX21 and cytokine levels and kinetics correlate better with CM than virulence phenotype. The earliest detection of BAG1 was seven days post infection. Only infection with the genotype of high CM (69.4%) was associated with high T-bet levels in the CLN 24 h and high systemic IFNγ expression which was sustained over the first week, while infection with genotypes of lower CM (38.8%, 10.7% and 6.8%) is characterized by down-regulation and/or low systemic levels of IFNγ. The response intensity, as assessed by cytokine levels, to the genotype of high CM wanes over time, while it increases gradually to genotypes of lower CM.
UNASSIGNED: The results point to the conclusion that the immune response is not correlated with the virulence phenotype and/or allele profile, but an early onset, intense pro-inflammatory response is characteristic of genotypes with high CM. Additionally, high IFNγ level in the brain may hamper stage conversion.
摘要：
■弓形虫是一种对人类和兽医健康至关重要的细胞内寄生虫。弓形虫基因型种群的结构和多样性在地理上有很大差异，但是三个血统，I型,II和III,分布在全球。谱系III基因型在生物学方面特征最差，宿主免疫力和毒力。一旦宿主感染了T.gondii,参与先天免疫机制以减少组织中的寄生虫负担,并创造促炎环境,在该环境中,TH1应答发展以确保存活.这项研究调查了Swiss-Webster小鼠腹膜内感染后的早期细胞免疫反应，该小鼠具有四种不同的非克隆基因型III和局部分离株ToxoDB＃1的10个速殖子。毒力表型，ROP5，ROP16，ROP18和GRA15的累积死亡率（CM）和等位基因谱先前已发表。
■通过实时PCR和IFNγ的相对表达水平分析寄生虫在不同组织中的传播，颈淋巴结（CLN）中的IL12-p40，IL-10和TBX21，使用ΔΔCt方法计算脑和脾。通过检测脑中的BAG1转录物确定阶段转化。
■组织播散取决于毒力表型，但不取决于CM，而TBX21和细胞因子水平和动力学与CM的相关性比毒力表型更好。BAG1的最早检测是感染后7天。只有高CM基因型（69.4％）的感染与CLN24h中的高T-bet水平和在第一周内持续的高全身IFNγ表达有关，而感染基因型较低的CM(38.8%，10.7％和6.8％）的特征在于IFNγ的下调和/或系统水平低。响应强度,通过细胞因子水平评估，随着时间的推移，高CM的基因型逐渐减弱，而逐渐增加到低CM的基因型。
■结果表明，免疫应答与毒力表型和/或等位基因谱无关，但是早期发作，强烈的促炎反应是高CM基因型的特征。此外,大脑中的高IFNγ水平可能会阻碍阶段转换。
■通过实时PCR和IFNγ的相对表达水平分析寄生虫在不同组织中的传播，颈淋巴结（CLN）中的IL12-p40，IL-10和TBX21，使用ΔΔCt方法计算脑和脾。通过检测脑中的BAG1转录物确定阶段转化。
■组织播散取决于毒力表型，但不取决于CM，而TBX21和细胞因子水平和动力学与CM的相关性比毒力表型更好。BAG1的最早检测是感染后7天。只有高CM基因型（69.4％）的感染与CLN24h中的高T-bet水平和在第一周内持续的高全身IFNγ表达有关，而感染基因型较低的CM(38.8%，10.7％和6.8％）的特征在于IFNγ的下调和/或系统水平低。响应强度,通过细胞因子水平评估，随着时间的推移，高CM的基因型逐渐减弱，而逐渐增加到低CM的基因型。
■结果表明，免疫应答与毒力表型和/或等位基因谱无关，但是早期发作，强烈的促炎反应是高CM基因型的特征。此外,大脑中的高IFNγ水平可能会阻碍阶段转换。
