title: Upregulated expression of Tim-3 involved in the process of toxoplasmic encephalitis in mouse model.
abstract: Toxoplasma gondii can establish chronic infection and is characterized by the formation of tissue cysts in the brain. The cysts may remain throughout the life of the host but can reactivate and cause life-threatening toxoplasmic encephalitis (TE) in immunocompromised patients. T cell-mediated immune responses are essential for preventing the reactivation of chronic infection of T. gondii in the brain. The immunoinhibitory receptor T cell immunoglobulin and mucin domain (Tim)-1 and Tim-3 are expressed on terminally differentiated T helper (Th) 2 and Th1 cells, respectively, participating in the regulation of Th immune response. However, there is no report concerning the role of Tim genes in TE. In this study, Kunming outbred mice were infected with Prugniaud (Pru), a type II strain of T. gondii by oral gavage. Compared with the uninfected controls, there were mild brain inflammations at 3 weeks postinfection (p.i.), moderate brain inflammations at 5 weeks p.i., and aggravated brain inflammations and necrosis at 7 and 9 weeks p.i. The expressions of tachyzoite stage-specific genes in brains were consistent with the severity of brain histopathology of TE at 5 and 7 weeks p.i., while the expressions of bradyzoite stage-specific genes in brains were significantly increased at 7 and 9 weeks p.i. Using quantitative real-time PCR detection and immunohistochemistry staining, our results showed that the expressions of Tim-3 were significantly upregulated in both brains and spleens at 5 weeks p.i. and in spleens at 9 weeks p.i., which showed the similar dynamic tendency as that of interferon-γ expressions in both brains and spleens at the same times. In contrast, the Th2-specific marker Tim-1 expressions were significantly downregulated in both brains and spleens at 3 weeks p.i. and upregulated in both brains and spleens at 7 and 9 weeks p.i., which showed the similar dynamic tendency as that of interleukin-4 expressions in both brains and spleens at the same time. Our data indicate that Tim-3 may involve in the process of TE in mice infected with T. gondii Pru strain.
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, Guangdong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Shaoyuan
authors.initials: S
authors.lastname: Li
authors.forename: Junping
authors.initials: J
authors.lastname: Yan
authors.forename: Huanqin
authors.initials: H
authors.lastname: Zheng
authors.forename: Shiguang
authors.initials: S
authors.lastname: Huang
authors.forename: Jilong
authors.initials: J
authors.lastname: Shen
authors.forename: Zhao-Rong
authors.initials: ZR
authors.lastname: Lun
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Lloyd H
authors.initials: LH
authors.lastname: Kasper
authors.forename: Fangli
authors.initials: F
authors.lastname: Lu
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D000072597:Hepatitis A Virus Cellular Receptor 2; D006651:Histocytochemistry; D007150:Immunohistochemistry; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D011991:Receptors, Virus / Q000235:genetics*; D013154:Spleen / Q000473:pathology; D014124:Toxoplasmosis, Animal / Q000473:pathology*; D016781:Toxoplasmosis, Cerebral / Q000473:pathology*; D015854:Up-Regulation
chemical_list: C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus