Expression of toll-like receptor 2, 4 and related cytokines in intraperitoneally inoculated Balb/C mice with Echinococcus multilocularis.
Expression of toll-like receptor 2, 4 and related cytokines in intraperitoneally inoculated Balb/C mice with Echinococcus multilocularis.
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腹腔接种多房棘球绦虫Balb/C小鼠体内Toll样受体2、4及相关细胞因子的表达。
DOI：
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Wen Hao
中科院分区：
文献类型：
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作者：
Shadike Apaer;Tuerhongjiang Tuxun;Ma Hai-Zhang;Zhang Heng;Zhang Hao;Jiangduosi Payiziwula;Zhao Pei-Ji;Aizimaiti Aihaiti;Li Tao;Zhao Jin-Ming;Lin Ren-Yong;Wen Hao
宿主与多房棘球绦虫之间的免疫应答模式被认为是泡状棘球绦虫病发生发展的关键环节。本研究旨在研究TLR2和TLR4及其相关细胞因子和转录因子在继发性多房棘球绦虫感染小鼠模型中的表达模式。用多房棘球菌胃内接种建立小鼠AE模型，第3个月开始经胃管给药阿苯达唑(E.m+ABZ组)或羧甲基纤维素组(CMC；E.m+CMC组)。给予CMC的小鼠为阴性对照(C+CMC组)。制备小鼠脾细胞和腹膜渗出物细胞(PECs)，用酶联免疫吸附试验(EL ISA)检测脾细胞和PECs培养上清液中干扰素-γ、IL-10和IL-5水平。采用实时荧光定量逆转录聚合酶链式反应(qRT-PCR)检测TLR2、TLR2、TL4、转录因子和细胞因子的mRNA表达水平。经刀豆蛋白A(ConA)刺激36h后，E.m+CMC组脾细胞和脾细胞培养上清液中γ、IL-10和IL-5的浓度均极低，而E.m+CMC组明显高于E.m+ABZ组和C+CMC组。与其他组比较，E.m+CMC组小鼠脾细胞TLR2、4mRNA及GATA3、γ、IL-10mRNA水平均显著升高。同时，E.m+ABZ组和C+CMC组T-bet mRNA的表达均高于E.m+CMC组。E.m+ABZ组T-bet/GATA3比值高于E.m+CMC组，C+CMC组高于E.m+CMC组。脾细胞TLR2基因表达与脾细胞培养上清液中IL-10浓度呈正相关。本研究为多房棘球绦虫感染过程中TLR2在免疫耐受过程中的可能作用提供了证据，并提示阿苯达唑治疗可能逆转免疫耐受状况，改善寄生虫清除过程。
Immune response pattern between host and Echinococcus multilocularis (E. multilocularis) is considered as a crucial point in development of alveolar echinococcosis (AE). In this study, we are aiming to study the expression patterns of TLR2 and TLR4 with related cytokines and transcription factors in secondary E. multilocularis infected murine model. The murine model of AE was developed by using intraperitoneal inoculation of E. multilocularis protoscolexes and albendazole (E. m+ABZ group) or carboxy methyle cellulose (CMC; E. m+CMC group) administration via gastric tube was initiated in the third month and continued for one month. Mice with CMC administration served as negative controls (C+CMC group). The splenic cells and peritoneal exudates cells (PECs) were prepared and the levels of IFN-γ, IL-10, and IL-5 in splenic cells and PECs culture supernatants were detected using enzyme linked immune-sorbent assay (ELISA). Besides, the mRNA expression levels of TLR2, 4, transcription factors and cytokines were detected by using real-time fluorescent quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The concentration levels of IFN-γ, IL-10, and IL-5 in PECs and splenic cell supernatants were extremely lower, however, significantly elevated after stimulated with Concanavalin A (ConA) for 36 h with higher concentrations in E. m+CMC group comparing to both E. m+ABZ and C+CMC group. The mRNA levels of TLR2, 4 and GATA3, IFN-γ, IL-10 in splenic cells were significantly increased in E. m+CMC group comparing with other groups. Simultaneously, T-bet mRNA expressions were elevated in E. m+ABZ and C+CMC group compared to E. m+CMC group. In addition, T-bet/GATA3 ratios was higher in E. m+ABZ group compared to E. m+CMC group and were higher in C+CMC group than those in E. m+CMC group. TLR2 mRNA expression in splenic cells showed a positive correlation with IL-10 concentration levels in splenic cell culture supernatants. The present study provides evidence on the possible role of TLR2 in the process of immune tolerance during E. multilocularis infection and suggests albendazole treatment might reverse the immune tolerance situation and improve parasite clearance process.
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