TLR2 deficiency leads to increased Th17 infiltrates in experimental brain abscesses.
TLR2 deficiency leads to increased Th17 infiltrates in experimental brain abscesses.
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DOI：
10.4049/jimmunol.0802656
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发表时间：
2009-06-01
期刊：
影响因子：
--
通讯作者：
Kielian T
中科院分区：
文献类型：
--
作者：
Nichols JR;Aldrich AL;Mariani MM;Vidlak D;Esen N;Kielian T
TLR 2在识别S.金黄色葡萄球菌是CNS实质感染如脑脓肿的常见病原体。我们先前报道了TLR 2基因敲除小鼠的脑水肿表现出IL-17水平升高，提示存在一种替代途径可用于响应S。金黄色葡萄球菌感染可能涉及Th 17细胞。与野生型动物相比，在感染后第3、7和14天，TLR 2 KO小鼠的脑水肿中CD 4+和CD 8 + T细胞浸润均升高。细胞内细胞因子染色显示，在IFN-γ阳性细胞相对较少的TLR 2 KO小鼠中，产生IL-17的Th 17细胞的频率显著增加，γδ T细胞也是脑水肿中IL-17的来源。显示小胶质细胞、星形胶质细胞和巨噬细胞表达IL-17 RA和IL-17 RC。尽管有受体表达，IL-17在引发胶质细胞活化方面相对无效，而细胞因子增强了TNF-α诱导巨噬细胞表达CXCL 2和CCL 2的能力。基于IL-17引发趋化因子和其他促炎介质释放的能力，我们提出，在TLR 2 KO小鼠中发生的过度IL-17反应以补偿方式发挥作用以控制脑脓肿发病机制，其中胶质细胞以外的细胞作为IL-17作用的靶点。这得到了我们的发现的支持，其中先天免疫浸润在TLR 2 KO和WT小鼠之间没有显著差异，并且在感染过程中缺乏其他促炎分子合成的长期改变。
TLR2 plays a pivotal role in recognizing S. aureus, a common etiologic agent of CNS parenchymal infections, such as brain abscess. We previously reported that brain abscesses of TLR2 knockout (KO) mice exhibited elevated IL-17 levels, suggesting the presence of an alternative pathway available to respond to S. aureus infection that may involve Th17 cells. Both CD4+ and CD8+ T cell infiltrates were elevated in brain abscesses of TLR2 KO mice at days 3, 7, and 14 post-infection compared to wild type animals. Intracellular cytokine staining revealed a significant increase in the frequency of IL-17-producing Th17 cells in TLR2 KO mice with relatively few IFN-γ-positive cells.γδ T cells were also a source of IL-17 in brain abscesses. Microglia, astrocytes, and macrophages were shown to express both IL-17RA and IL-17RC. Despite receptor expression, IL-17 was relatively ineffective at eliciting glial activation, whereas the cytokine augmented the ability of TNF-α to induce CXCL2 and CCL2 expression by macrophages. Based on the ability of IL-17 to elicit the release of chemokines and other pro-inflammatory mediators, we propose that the exaggerated IL-17 response that occurs in TLR2 KO mice functions in a compensatory manner to control brain abscess pathogenesis, with cells other than glia as targets for IL-17 action. This is supported by our findings where innate immune infiltrates were not significantly different between TLR2 KO and WT mice in conjunction with the lack of prolonged alterations in the synthesis of other pro-inflammatory molecules during the course of infection.
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影响因子：
64.5
作者：
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作者：
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