Early immune responses and parasite tissue distribution in mice experimentally infected with oocysts of either archetypal or non-archetypal genotypes of Toxoplasma gondii
Early immune responses and parasite tissue distribution in mice experimentally infected with oocysts of either archetypal or non-archetypal genotypes of Toxoplasma gondii
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DOI：
10.1017/s0031182020002346
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发表时间：
2021-04-01
期刊：
影响因子：
2.4
通讯作者：
Katzer, Frank
中科院分区：
文献类型：
--
作者：
Chiebao, Daniela P.;Bartley, Paul M.;Katzer, Frank
在世界上大多数地区，弓形虫由原型型（I型、II型和III型）组成;然而，南美洲显示出几种非原型株。本研究使用实验小鼠模型来表征不同寄生虫基因型感染后的免疫应答和寄生虫动力学。每只小鼠口服接种50个T.对于组（G）2、G3和G4，分别使用弓形虫M4 II型（原型，无毒力）、BrI或BrIII（分别为非原型，毒性和中等毒性）。通过SYBR绿色逆转录-定量聚合酶链反应定量细胞因子、免疫化合物、细胞表面标志物和受体衔接子[干扰素γ（IFN γ）、白细胞介素（IL）-12、CD 8、CD 4、CD 25、CXCR 3和MyD 88]的mRNA表达水平。病变的特点是组织学和免疫组化检测建立寄生虫的分布。G2小鼠的感染是轻微的，其特征在于早期MyD 88依赖性途径。在G3中，在感染后8-11天（dpi）表现出严重临床症状的小鼠中存在促炎细胞因子IFN γ和IL-12的高水平表达，结合CD 25的上调、丰富的速殖子和肝、肺和肠中的组织病变。IFN γ和IL-12基因的显著更长的表达，以及其他Th 1平衡的免疫应答，例如G4中CXCR 3和MyD 88水平的增加，导致小鼠存活和慢性弓形虫病，在14和21 dpi时在脑和肺中发生组织囊肿。不同的免疫应答和基因表达动力学似乎是由不同的菌株引起的，并且非原型寄生虫表现出更高的毒力。
In most of the world Toxoplasma gondii is comprised of archetypal types (types I, II and III); however, South America displays several non-archetypal strains. This study used an experimental mouse model to characterize the immune response and parasite kinetics following infection with different parasite genotypes. An oral inoculation of 50 oocysts per mouse from T. gondii M4 type II (archetypal, avirulent), BrI or BrIII (non-archetypal, virulent and intermediate virulent, respectively) for groups (G)2, G3 and G4, respectively was used. The levels of mRNA expression of cytokines, immune compounds, cell surface markers and receptor adapters [interferon gamma (IFN gamma), interleukin (IL)-12, CD8, CD4, CD25, CXCR3 and MyD88] were quantified by SYBR green reverse transcription-quantitative polymerase chain reaction. Lesions were characterized by histology and detection by immunohistochemistry established distribution of parasites. Infection in G2 mice was mild and characterized by an early MyD88-dependent pathway. In G3, there were high levels of expression of pro-inflammatory cytokines IFN gamma and IL-12 in the mice showing severe clinical symptoms at 8-11 days post infection (dpi), combined with the upregulation of CD25, abundant tachyzoites and tissue lesions in livers, lungs and intestines. Significant longer expression of IFN gamma and IL-12 genes, with other Th1-balanced immune responses, such as increased levels of CXCR3 and MyD88 in G4, resulted in survival of mice and chronic toxoplasmosis, with the occurrence of tissue cysts in brain and lungs, at 14 and 21 dpi. Different immune responses and kinetics of gene expression appear to be elicited by the different strains and non-archetypal parasites demonstrated higher virulence.