Yang Jing, Du Fen, Zhou Xiaoliu, Wang Lixia, Li Senyang, Fang Rui, Zhao Junlong
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China.
Hubei Centre for Animal Diseases Control and Prevention, Wuhan, 430070, Hubei, People's Republic of China.
Parasitol Res. 2018 Aug;117(8):2623-2633. doi: 10.1007/s00436-018-5954-z. Epub 2018 Jun 12.
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, Ca- and metabolism-related proteins were upregulated in C vs D, which supported the hypothesis that CD44 mediated the production of host Ca and IFN-γ 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.
慢性临床弓形虫感染是导致严重脑炎的主要疾病状态。CD44是细胞粘附分子家族的成员，在弓形虫感染中起重要作用。然而，关于慢性弓形虫感染期间CD44的蛋白质组学变化鲜有报道。因此，进行了一项基于iTRAQ的蛋白质组学研究，并结合二维液相色谱-串联质谱分析，以筛选慢性弓形虫感染期间与CD44相关的蛋白质。结果，共可靠鉴定和定量了2612种蛋白质。随后，比较了CD44基因敲除小鼠（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基因敲除小鼠（D）之间的259种、106种和249种差异表达蛋白（DEP）。对这些差异表达蛋白进行了基因本体论、KEGG通路和蛋白质-蛋白质相互作用分析。结果显示，在A与B、B与C以及C与D的比较中，免疫相关蛋白发生了显著变化，这可能表明慢性弓形虫感染导致宿主免疫反应发生改变。此外，C与D比较中钙和代谢相关蛋白上调，这支持了CD44介导宿主钙和干扰素-γ产生以及寄生虫优先侵入高表达CD44细胞的假说。本研究结果验证并加深了对CD44在慢性弓形虫感染宿主中作用的全面认识，从而为未来关于CD44在潜伏性弓形虫病中具体功能的研究提供了新思路。
