Involvement of Toll-like receptor 2 in the cerebral immune response and behavioral changes caused by latent Toxoplasma infection in mice
Involvement of Toll-like receptor 2 in the cerebral immune response and behavioral changes caused by latent Toxoplasma infection in mice
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DOI：
10.1371/journal.pone.0220560
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发表时间：
2019-08-12
期刊：
影响因子：
3.7
通讯作者：
Nishikawa, Yoshifumi
中科院分区：
文献类型：
--
作者：
Ihara, Fumiaki;Tanaka, Sachi;Nishikawa, Yoshifumi
亚急性和慢性感染的细胞内原生动物寄生虫弓形虫与精神疾病的风险增加，如精神分裂症。然而，T. gondii引起的神经元紊乱最近，我们报道了Toll样受体2（TLR 2）在培养的小鼠脑细胞中启动先天性免疫反应所必需的。然而，TLR 2如何参与T.弓形虫感染仍不清楚。因此，我们使用野生型（TLR 2（+/+））和TLR 2缺陷型（TLR 2（-/-））小鼠检测TLR 2在脑病理学和行为中的作用。行为学分析表明，TLR 2缺陷增加了未感染和感染动物的焦虑状态，TLR 2缺陷与感染无关。在情境和线索恐惧条件反射测试中，T。弓形虫感染可降低小鼠的冻结反应，而TLR 2缺乏可增强小鼠的冻结反应，但二者之间无交互作用。我们的组织病理学分析表明，TLR 2（+/+）和TLR 2（-/-）小鼠在感染T.刚地。在30 dpi时，在TLR 2（-/-）小鼠的脑中检测到的寄生虫数量高于TLR 2（+/+）小鼠的脑中检测到的寄生虫数量，但在7和14 dpi时没有。在TLR 2（+/+）和TLR 2（-/-）小鼠中未观察到促炎基因表达水平的显著差异。因此，脑中的TLR 2信号传导可能有助于控制寄生虫生长，但不影响脑病理学或由T.刚地。
Subacute and chronic infections with the intracellular protozoan parasite Toxoplasma gondii are associated with an increased risk of psychiatric diseases like schizophrenia. However, little is known about the mechanisms involved in T. gondii-induced neuronal disorders. Recently, we reported that Toll-like receptor 2 (TLR2) was required to initiate the innate immune response in cultured mouse brain cells. However, how TLR2 contributes to latent infection with T. gondii remains unclear. Therefore, we examined the role of TLR2 in brain pathology and behavior using wild-type (TLR2(+/+)) and TLR2-deficient (TLR2(-/-)) mice. The behavioral analyses showed that TLR2 deficiency increased the anxiety state of the uninfected and infected animals alike, and TLR2 deficiency showed no relationship with the infection. In the contextual and cued fear-conditioning tests, T. gondii infection decreased the mouse freezing reaction while TLR2 deficiency increased it, but there was no interaction between the two factors. Our histopathological analysis showed that the TLR2(+/+) and TLR2(-/-) mice had similar brain lesions at 30 days post infection (dpi) with T. gondii. Higher numbers of parasites were detected in the brains of the TLR2(-/-) mice than in those from the TLR2(+/+) mice at 30 dpi, but not at 7 and 14 dpi. No significant differences were observed in the proinflammatory gene expression levels in the TLR2(+/+) and TLR2(-/-) mice. Therefore, it appears that TLR2 signaling in the brain might contribute to the control of parasite growth, but not to brain pathology or the impaired fear memory response induced by infection with T. gondii.