Astrocytic TGF-β signaling limits inflammation and reduces neuronal damage during central nervous system Toxoplasma infection.
Astrocytic TGF-β signaling limits inflammation and reduces neuronal damage during central nervous system Toxoplasma infection.
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DOI：
10.4049/jimmunol.1303284
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发表时间：
2014-07-01
期刊：
影响因子：
--
通讯作者：
Buckwalter MS
中科院分区：
文献类型：
--
作者：
Cekanaviciute E;Dietrich HK;Axtell RC;Williams AM;Egusquiza R;Wai KM;Koshy AA;Buckwalter MS
在大脑中，控制感染和限制炎症之间的平衡尤其不稳定，因为大脑对炎症的毒性作用具有独特的脆弱性。在中枢神经系统感染中，包括刚地弓形虫（一种原生动物寄生虫，在小鼠和人类中自然会建立慢性中枢神经系统感染）感染，星形胶质细胞被认为是神经炎症的关键调节因子。在中枢神经系统弓形虫病中，星形胶质细胞对控制寄生虫生长至关重要。它们分泌促炎细胞因子并在物理上包围寄生虫。然而，星形胶质细胞在弓形虫脑炎期间用于限制神经炎症的分子机制尚未确定。星形胶质细胞中的转化生长因子β（TGFβ）信号传导特别令人关注，因为TGFβ在中枢神经系统感染期间普遍上调，并具有主要的调节和抗炎功能。我们在此报告，在弓形虫脑炎期间，星形胶质细胞中的TGFβ信号传导被激活，并且抑制星形胶质细胞的TGFβ信号传导会增加免疫细胞浸润，使促炎因子和趋化因子的产生与中枢神经系统寄生虫负荷脱钩，并增加神经元损伤。值得注意的是，我们表明抑制星形胶质细胞TGFβ信号传导的影响与寄生虫负荷以及GFAP +星形胶质细胞在物理上包围寄生虫的能力无关。
The balance between controlling infection and limiting inflammation is particularly precarious in the brain because of its unique vulnerability to the toxic effects of inflammation. Astrocytes have been implicated as key regulators of neuroinflammation in CNS infections, including infection with Toxoplasma gondii, a protozoan parasite that naturally establishes a chronic CNS infection in mice and humans. In CNS toxoplasmosis, astrocytes are critical to controlling parasite growth. They secrete pro-inflammatory cytokines and physically encircle parasites. However, the molecular mechanisms used by astrocytes to limit neuroinflammation during toxoplasmic encephalitis have not yet been identified. Transforming growth factor beta (TGFβ) signaling in astrocytes is of particular interest because TGFβ is universally upregulated during CNS infection and serves master regulatory and primarily anti-inflammatory functions. We report here that TGFβ signaling is activated in astrocytes during toxoplasmic encephalitis, and that inhibition of astrocytic TGFβ signaling increases immune cell infiltration, uncouples pro-inflammatory and chemokine production from CNS parasite burden, and increases neuronal injury. Remarkably, we show that the effects of inhibiting astrocytic TGFβ signaling are independent of parasite burden and the ability of GFAP+ astrocytes to physically encircle parasites.
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影响因子：
16.8
作者：
Appay, V;Rowland-Jones, SL
通讯作者：
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影响因子：
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作者：
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DOI：
10.1523/jneurosci.5648-11.2012
发表时间：
2012-01-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
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影响因子：
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影响因子：
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