Predominant Interferon-γ-Mediated Expression of CXCL9, CXCL10, and CCL5 Proteins in the Brain During Chronic Infection with Toxoplasma gondii in BALB/c Mice Resistant to Development of Toxoplasmic Encephalitis
Predominant Interferon-γ-Mediated Expression of CXCL9, CXCL10, and CCL5 Proteins in the Brain During Chronic Infection with Toxoplasma gondii in BALB/c Mice Resistant to Development of Toxoplasmic Encephalitis
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DOI：
10.1089/jir.2009.0119
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发表时间：
2010-09-01
影响因子：
2.3
通讯作者：
Suzuki, Yasuhiro
中科院分区：
文献类型：
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作者：
Wen, Xiangshu;Kudo, Tomoya;Suzuki, Yasuhiro
我们使用BALB/c和BALB/c背景IFN-γ基因敲除（IFN-γ（-/-））小鼠检测了慢性弓形虫感染期间IFN-γ在脑中趋化因子mRNA和蛋白表达中的作用。BALB/c小鼠对弓形体脑炎的发展具有遗传抗性，并通过IFN-γ介导的免疫应答在脑中建立潜伏的慢性感染。感染后，野生型小鼠脑中CXCL 9/RANTES、CXCL 10/IP-10、CXCL 11/I-TAC、CCL 2/MCP-1、CCL 3/MIP-1 α和CCL 5/RANTES的mRNA量显著增加。在这些趋化因子中，CXCL 9/RANTES、CXCL 10/IP-10和CCL 5/RANTES mRNA最丰富。感染后，在IFN-γ（-/-）小鼠的脑中也观察到CXCL 10/IP-10、CCL 2/MCP-1、CCL 3/MIP-1 α和CCL 5/RANTES的mRNA量增加，尽管感染的IFN-γ（-/-）小鼠中的CXCL 10/I-10和CCL 5/RANTES mRNA水平显著低于感染的野生型动物。在感染IFN-γ（-/-）小鼠中，CXCL 9/I-TAC和CXCL 11/I-TAC的mRNA量保持在基础水平。当在两种品系的未感染和感染小鼠的脑匀浆中检查趋化因子蛋白的量时，仅在感染的野生型动物中检测到大量的CXCL 9/RANTES、CXCL 10/IP-10和CCL 5/RANTES。这些结果表明，CXCL 9/RANTES、CXCL 10/IP-10和CCL 5/RANTES是在T.它们的表达依赖于IFN-γ。
We examined the role of interferon-gamma (IFN-gamma) in expression of chemokine mRNA and proteins in the brain during chronic infection with Toxoplasma gondii using BALB/c and BALB/c-background IFN-gamma knockout (IFN-gamma(-/-)) mice. BALB/c mice are genetically resistant to development of toxoplasmic encephalitis and establish a latent, chronic infection in the brain through IFN-gamma-mediated immune responses. Amounts of mRNA for CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC, CCL2/MCP-1, CCL3/MIP-1 alpha, and CCL5/RANTES significantly increased in the brains of wild-type mice after infection. CXCL9/MIG, CXCL10/IP-10, and CCL5/RANTES mRNA were most abundant among these chemokines. An increase in amounts of mRNA for CXCL10/IP-10, CCL2/MCP-1, CCL3/MIP-1 alpha, and CCL5/RANTES was also observed in the brains of IFN-gamma(-/-) mice after infection, although CXCL10/I-10 and CCL5/RANTES mRNA levels in infected IFN-gamma(-/-) mice were significantly lower than those of infected wild-type animals. Amounts of mRNA for CXCL9/MIG and CXCL11/I-TAC remained at the basal levels in infected IFN-gamma(-/-) mice. When amounts of the chemokine proteins were examined in the brain homogenates of uninfected and infected mice of both strains, large amounts of CXCL9/MIG, CXCL10/IP-10, and CCL5/RANTES were detected only in infected wild-type animals. These results indicate that CXCL9/MIG, CXCL10/IP-10, and CCL5/RANTES are the chemokines predominantly induced in the brains of genetically resistant BALB/c mice during chronic infection with T. gondii, and their expression is dependent on IFN-gamma.