IL-33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii
IL-33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii
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DOI：
10.1002/eji.200939705
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发表时间：
2010-02-01
影响因子：
5.4
通讯作者：
Roberts, Craig W.
中科院分区：
文献类型：
--
作者：
Jones, Leigh A.;Roberts, Fiona;Roberts, Craig W.
T1/ST 2是IL-1受体家族的免疫调节蛋白，最近报道其为IL-33受体的组分。IL-33是一种新描述的细胞因子，已知其可放大Th 2应答并减少Th 1细胞因子的产生。T1/ST 2在弓形虫感染过程中的作用尚不清楚。考虑到有效控制寄生虫数量和免疫病理学需要平衡的1型/2型反应，T1/ST 2可能在帮助这一过程中发挥作用。因此，我们已经表明，T1/ST 2 mRNA转录上调，在小鼠的大脑中感染T。T1/ST 2缺陷小鼠对弓形虫感染的易感性增加。弓形虫，与增加病理和更大的寄生虫负担的大脑。脑细胞因子水平的实时PCR分析显示，在感染的T1/ST 2（-/-）小鼠中，iNOS、IFN-γ和TNF-α的mRNA水平增加。这些作用独立于IL-10产生的变化。这项研究提供了IL-33受体信号传导在大脑中的特定作用的第一个证据，并强调了这种机制在限制细胞内寄生虫感染方面的要求。
T1/ST2 is an immunoregulatory protein of the IL-1 receptor family that has recently been reported as being a component of the IL-33 receptor. IL-33 is a newly described cytokine known to amplify the Th2 response and reduce production of Th1 cytokines. The function of T1/ST2 during Toxoplasma gondii infection is as yet undescribed. Given the requirement of a balanced type 1/type 2 response for effective control of parasite number and immunopathology, it is likely that T1/ST2 may play a part in aiding this process. Accordingly, we have shown that T1/ST2 mRNA transcripts are upregulated in the brains of mice infected with T. gondii and that mice deficient in T1/ST2 demonstrated increased susceptibility to infection with T. gondii that correlated with increased pathology and greater parasite burden in the brains. Real-time PCR analysis of cerebral cytokine levels revealed increased mRNA levels of iNOS, IFN-gamma and TNF-alpha in infected T1/ST2(-/-) mice. These effects were independent of changes in IL-10 production. This study provides the first evidence of a specific role for IL-33 receptor signalling in the brain as well as highlighting the requirement of this mechanism in limiting infection with an intracellular parasite.