Brain proteomic differences between wild-type and CD44-mice induced by chronic Toxoplasma gondii infection
Brain proteomic differences between wild-type and CD44-mice induced by chronic Toxoplasma gondii infection
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慢性弓形虫感染诱导的野生型和CD44-小鼠脑蛋白质组差异
DOI：
10.1007/s00436-018-5954-z
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发表时间：
2018-08-01
影响因子：
2
通讯作者：
Zhao, Junlong
中科院分区：
文献类型：
--
作者：
Yang, Jing;Du, Fen;Zhao, Junlong
慢性临床弓形虫（T. gondii）感染是引起重症脑炎的原发病状态。 CD44是细胞粘附分子家族的成员，在弓形虫感染中发挥重要作用。然而，慢性弓形虫感染期间CD44的蛋白质组变化却鲜有报道。因此，进行了基于 iTRAQ 的蛋白质组学研究与 2D-LC-MS/MS 分析相结合，以筛选慢性弓形虫感染期间的 CD44 相关蛋白。结果，总共 2612 种蛋白质被可靠地鉴定和定量。随后，比较了 CD44- 小鼠 (A) 与野生型小鼠 (B)、B 与感染弓形虫的野生型小鼠 (C) 以及 C 与感染弓形虫的 CD44- 小鼠 (D) 之间的 259、106 和 249 个差异表达蛋白 (DEP)。对 DEP 进行基因本体论、KEGG 通路和蛋白质-蛋白质相互作用分析。结果显示，A与B、B与C、C与D比较中免疫相关蛋白发生了显着改变，这可能表明慢性弓形虫感染引起了宿主免疫反应的变化。此外，C 与 D 中的 Ca2+- 和代谢相关蛋白上调，这支持了以下假设：CD44 介导宿主 Ca2+ 和 IFN-γ 的产生，并且寄生虫优先侵入表达高水平 CD44 的细胞。本研究结果验证并使得人们能够更全面地了解CD44在慢性弓形虫感染宿主中的作用，从而为未来研究CD44在潜伏性弓形虫病中的特定功能提供新思路。
Chronic clinical Toxoplasma gondii (T. gondii) infection is the primary disease state that causes severe encephalitis. CD44 is a member of the cell adhesion molecule family and plays an important role in T. gondii infection. However, proteomic changes in CD44 during chronic T. gondii infection have rarely been reported. Thus, an iTRAQ-based proteomic study coupled with 2D-LC-MS/MS analysis was performed to screen CD44-related proteins during chronic T. gondii infection. As a result, a total of 2612 proteins were reliably identified and quantified. Subsequently, 259, 106, and 249 differentially expressed proteins (DEPs) were compared between CD44- mice (A) vs wild-type mice (B), B vs wild-type mice infected with T. gondii (C), and C vs CD44- mice infected with T. gondii (D). Gene ontology, KEGG pathway, and protein-protein interaction analyses were performed on the DEPs. According to the results, immune-related proteins were altered significantly among the A vs B, B vs C, and C vs D comparisons, which might indicate that chronic T. gondii infection caused changes in the host immune response. Additionally, Ca2+- and metabolism-related proteins were upregulated in C vs D, which supported the hypothesis that CD44 mediated the production of host Ca2+ and IFN-gamma and that the parasite preferentially invaded cells expressing high levels of CD44. The present findings validate and enable a more comprehensive knowledge of the role of CD44 in hosts chronically infected with T. gondii, thus providing new ideas for future studies on the specific functions of CD44 in latent toxoplasmosis.