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Synergistic Toll-like Receptor 3/9 Signaling Affects Properties and Impairs Glioma-Promoting Activity of Microglia

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收录情况： ◇ SCIE ◇ 自然指数

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单位： [1]Helmholtz Assoc, Max Delbruck Ctr Mol Med, Cellular Neurosci, D-13125 Berlin, Germany [2]Charite, D-10117 Berlin, Germany [3]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Dept Neurosurg,Wuhan 430030,Hubei,Peoples R China [4]Univ Med Ctr Schleswig Holstein, Dept Neurosurg, D-24105 Kiel, Germany [5]Charite, Inst Cell Biol & Neurobiol, Dept Neurol, D-10117 Berlin, Germany [6]Johns Hopkins Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA [7]Charite Univ Med Berlin, Dept Radiol, D-13353 Berlin, Germany [8]Free Univ Berlin, D-13353 Berlin, Germany [9]Humboldt Univ, D-13353 Berlin, Germany [10]Berlin Inst Hlth, D-13353 Berlin, Germany

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关键词： brain macrophage costimulation glioma microglia Toll-like receptor 3 Toll-like receptor 9

摘要：

In murine experimental glioma models, TLR3 or TLR9 activation of microglial/macrophages has been shown to impair glioma growth, which could, however, not been verified in recent clinical trials. We therefore tested whether combined TLR3 and TLR9 acti-vation of microglia/macrophages would have a synergistic effect. Indeed, combined TLR3/TLR9 activation augmented the suppression of glioma growth in organotypic brain slices from male mice in a microglia-dependent fashion, and this synergistic suppression depended on interferon b release and phagocytic tumor clearance. Combined TLR3/TLR9 stimulation also augmented several func-tional features of microglia, such as the release of proinflammatory factors, motility, and phagocytosis activity. TLR3/TLR9 stimulation combined with CD47 blockade further augmented glioma clearance. Finally, we confirmed that the coactivation of TLR3/TLR9 also augments the impairment of glioma growth in vivo. Our results show that combined activation of TLR3/TLR9 in microglia/macro-phages results in a more efficient glioma suppression, which may provide a potential strategy for glioma treatment.

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出版当年[2019]版：

大类 | 2 区

医学

小类 | 2 区神经科学

最新[2025]版：

大类 | 2 区

医学

小类 | 2 区神经科学

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出版当年[2018]版：

Q1 NEUROSCIENCES

最新[2023]版：

Q1 NEUROSCIENCES

影响因子： 4.4 最新[2023版] 5.3 最新五年平均 6.074 出版当年[2018版] 6.485 出版当年五年平均 5.971 出版前一年[2017版] 5.674 出版后一年[2019版]

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第一作者单位： [1]Helmholtz Assoc, Max Delbruck Ctr Mol Med, Cellular Neurosci, D-13125 Berlin, Germany [2]Charite, D-10117 Berlin, Germany

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