Risk Assessment of Etanercept in Mice Chronically Infected With Toxoplasma gondii
Risk Assessment of Etanercept in Mice Chronically Infected With Toxoplasma gondii
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依那西普对弓形虫慢性感染小鼠的风险评估
DOI：
10.3389/fmicb.2018.02822
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发表时间：
2018-11
影响因子：
5.2
通讯作者：
Rui Fang
中科院分区：
文献类型：
--
作者：
Jing Yang;Luyao Wang;Dongmei Xu;Ding Tang;Senyang Li;Fen Du;Lixia Wang;Junlong Zhao;Rui Fang
弓形虫（Toxoplasma gondii，T.弓形虫）是一种严重危害宿主健康的人畜共患寄生虫。T.如果个体免疫力低下或有缺陷，弓形虫可以从缓殖子重新激活为速殖子，从而引起致命的弓形虫病。寄主对T.弓形虫感染通过介导Th 1型细胞免疫产生促炎细胞因子。肿瘤坏死因子（TNF）是一种重要的促炎细胞因子，可诱导寄生虫空泡（PV）的溶酶体融合而杀死寄生虫。依那西普是一种可溶性肿瘤坏死因子受体融合蛋白，临床上广泛用于治疗自身免疫性疾病。依那西普治疗自身免疫性疾病和慢性弓形虫病合并感染患者的效果和具体分子机制很少报道。在我们的研究中，建立了T.弓形虫感染的小鼠巨噬细胞RAW264.7细胞;目的：探讨依那西普对慢性弓形虫感染的影响。测定细胞因子水平并进行一系列的体内外表型实验。本研究发现，慢性感染T.用依那西普治疗后，体内实验证实，依那西普引起小鼠免疫水平下降，激活脑囊肿，将导致慢性感染转化为急性感染，引起严重的临床和病理症状。用依那西普预处理小鼠巨噬细胞RAW 264.7，然后用T.刚地。在体外实验中，细胞因子的表达水平降低，说明依那西普也能降低细胞的免疫力，促进缓殖子向速殖子转化，但不影响速殖子的细胞内复制。总之，依那西普治疗可通过降低体内和体外宿主免疫力来激活缓殖子向速殖子的转化。本研究获得的结果表明，在自身免疫性疾病和慢性弓形虫病合并感染的患者中使用依那西普可能导致慢性感染激活的风险，从而导致严重的急性弓形虫病。
Toxoplasma gondii (T. gondii) is a zoonotic parasite that severely harms the health of the host. The cysts of T. gondii can reactivate from bradyzoites to tachyzoites, if the individual develops low or defective immunity, causing lethal toxoplasmosis. The host resists T. gondii infection by mediating Th1-type cellular immunity to generate pro-inflammatory cytokines. Tumor necrosis factor (TNF) is an important pro-inflammatory cytokine, which can induce lysosomal fusion of parasitophorous vacuole (PV) to kill parasites. Etanercept is a soluble TNF receptor fusion protein, which is widely used clinically to cure autoimmune diseases. The effects and specific molecular mechanisms of etanercept treatment on patients co-infected with autoimmune diseases and chronic toxoplasmosis are rarely reported. In our study, a mouse model of chronic infection with T. gondii and murine macrophages RAW264.7 cells infected with T. gondii were employed to investigate the impact of etanercept on the status of chronic infection. The cytokines levels and a series of phenotypic experiments in vivo and in vitro were measured. In the present study, the expression levels of TNF, IL-1β, and IL-6 were decreased and the brain cysts number was increased in mice chronically infected with T. gondii after being treated with etanercept. In vivo experiments confirmed that etanercept caused a decrease in the immune levels of the mice and activated the brain cysts, which would lead to conversion from chronic infection to acute infection, causing severe clinical and pathological symptoms. Murine macrophages RAW264.7 cells were pretreated with etanercept, and then infected with T. gondii. In vitro experiments, the expression levels of cytokines were decreased, indicating that etanercept could also reduce the cells’ immunity and promote the transformation of bradyzoites to tachyzoites, but did not affect the intracellular replication of tachyzoites. In summary, etanercept treatment could activate the conversion of bradyzoites to tachyzoites through reducing host immunity in vivo and in vitro. The results obtained from this study suggest that the use of etanercept in patients co-infected with autoimmune diseases and chronic toxoplasmosis may lead to the risk of activation of chronic infection, resulting in severe acute toxoplasmosis.
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ANK1 和 DnaK-TPR，两种主要在弓形虫缓殖子中表达的含有四肽重复序列的蛋白质，对缓殖子分化没有贡献
影响因子：
5.2
作者：
Yang J;Zhang L;Diao H;Xia N;Zhou Y;Zhao J;Shen B
通讯作者：
Shen B
影响因子：
3.5
作者：
M. González-Vicent;M. Díaz;J. Sevilla;L. Madero
通讯作者：
M. González-Vicent;M. Díaz;J. Sevilla;L. Madero
DOI：
10.1051/parasite/2018014
发表时间：
2018
期刊：
Parasite (Paris, France)
影响因子：
--
作者：
Dégbé M;Debierre-Grockiego F;Tété-Bénissan A;Débare H;Aklikokou K;Dimier-Poisson I;Gbeassor M
通讯作者：
Gbeassor M
影响因子：
4
作者：
Lüder, CGK;Algner, M;Gross, U
通讯作者：
Gross, U
影响因子：
1.9
作者：
de Paula Rodrigues, Kelly Fernandes;Faria e Arantes, Tiago Eugenio;Pinheiro, Marcelo M.
通讯作者：
Pinheiro, Marcelo M.