B7-H3 Participates in the Development of Experimental Pneumococcal Meningitis by Augmentation of the Inflammatory Response via a TLR2-Dependent Mechanism
B7-H3 Participates in the Development of Experimental Pneumococcal Meningitis by Augmentation of the Inflammatory Response via a TLR2-Dependent Mechanism
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B7-H3 通过 TLR2 依赖性机制增强炎症反应，参与实验性肺炎球菌脑膜炎的发展
DOI：
10.4049/jimmunol.1103715
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发表时间：
2012-07-01
影响因子：
4.4
通讯作者：
Feng, Xing
中科院分区：
文献类型：
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作者：
Chen, Xuqin;Quinn, Edel M.;Feng, Xing
除了在调节T细胞介导的免疫应答中的充分记录的作用之外，B7-H3，B7超家族的新发现的成员，最近已被鉴定为先天免疫介导的炎症应答中的共刺激物。在这项研究中，我们进一步报告说，B7-H3参与肺炎球菌脑膜炎的发展在小鼠模型。外源性给予B7-H3强烈放大了炎症反应，加剧了血脑屏障破坏，并加重了肺炎链球菌感染的C3 H/HeN野生型小鼠的临床疾病状态。与体内研究结果一致，B7-H3显著增加促炎细胞因子和趋化因子的产生，上调NF-κ B p65和MAPK p38磷酸化，并增强NF-κ B p65在TNF-α和IL-6启动子处的核反式激活。肺炎刺激的原代鼠小胶质细胞。这些B7-H3相关的体外和体内效应似乎依赖于TLR 2信号传导，因为B7-H3在TLR 2缺陷型小胶质细胞和TLR 2缺陷型小鼠中几乎完全丧失了其扩增作用。此外，抗B7-H3 mAb（MIH 35）的给药减轻了S.肺炎感染的野生型小鼠。总之，我们的结果表明，B7-H3在S.肺炎感染引起的细菌性脑膜炎。免疫学杂志，2012，189：347-355。
In addition to a well-documented role in regulating T cell-mediated immune responses, B7-H3, a newly discovered member of the B7 superfamily, has been recently identified as a costimulator in the innate immunity-mediated inflammatory response. In this study, we further report that B7-H3 participates in the development of pneumococcal meningitis in a murine model. Exogenous administration of B7-H3 strongly amplified the inflammatory response, exacerbated blood-brain barrier disruption, and aggravated the clinical disease status in Streptococcus pneumoniae-infected C3H/HeN wild-type mice. Consistent with the in vivo findings, B7-H3 substantially augmented proinflammatory cytokine and chemokine production, upregulated NF-kappa B p65 and MAPK p38 phosphorylation, and enhanced the nuclear transactivation of NF-kappa B p65 at both TNF-alpha and IL-6 promoters in S. pneumoniae-stimulated primary murine microglia cells. These B7-H3-associated in vitro and in vivo effects appeared to be dependent on TLR2 signaling, as B7-H3 almost completely lost its amplifying actions in both TLR2-deficient microglial cells and TLR2-deficient mice. Furthermore, administration of the anti-B7-H3 mAb (MIH35) attenuated the inflammatory response and ameliorated blood-brain barrier disruption in S. pneumoniae-infected wild-type mice. Collectively, our results indicate that B7-H3 plays a contributory role in the development of S. pneumoniae infection-induced bacterial meningitis. The Journal of Immunology, 2012, 189: 347-355.