MyD88 is pivotal for immune recognition of Citrobacter koseri and astrocyte activation during CNS infection.
MyD88 is pivotal for immune recognition of Citrobacter koseri and astrocyte activation during CNS infection.
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DOI：
10.1186/1742-2094-8-35
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发表时间：
2011-04-16
影响因子：
9.3
通讯作者：
Kielian T
中科院分区：
文献类型：
--
作者：
Liu S;Kielian T
克氏柠檬酸杆菌（Citrobacter koseri）C. Koseri）是一种革兰氏阴性细菌，可引起高度侵袭性的新生儿脑膜炎，其通常进展为建立多灶性脑脓肿。Toll样受体4（TLR 4）及其信号接头MyD 88在中枢神经系统C. koseri感染尚未被研究，这是重要的，因为最近的证据表明，先天免疫反应是针对特定的病原体类别。在此，TLR 4 WT（C3 H/FeJ）和TLR 4突变体（C3 H/HeJ）小鼠以及MyD 88 KO动物用活的C. koseri，导致脑膜炎和脑室炎，伴随脑脓肿形成。MyD 88 KO小鼠对C. koseri，表明与WT动物相比，死亡率提高，细菌负荷显著升高。有趣的是，尽管早期促炎介质释放（即12小时）是MyD 88依赖性的，但MyD 88非依赖性信号传导的作用在24小时时是明显的，揭示了对CNS C的代偿反应。科塞里感染。与此相反，TLR 4并没有显着影响细菌负荷或促炎介质的生产响应C。koseri。在原代星形胶质细胞中也获得了类似的发现，其中MyD 88依赖性途径对于响应完整C. koseri，而TLR 4则为阴性;这暗示了替代性TLR的参与，因为高度富集的星形胶质细胞在细菌暴露后不产生IL-1，这也通过MyD 88发出信号。总的来说，这些发现证明了MyD 88依赖性机制在CNS C期间引发最大促炎反应、星形胶质细胞活化和细菌遏制方面的重要性。koseri感染，以及晚期MyD 88独立的细胞因子/趋化因子产生的信号通路。
Citrobacter koseri (C. koseri) is a Gram-negative bacterium that can cause a highly aggressive form of neonatal meningitis, which often progresses to establish multi-focal brain abscesses. The roles of Toll-like receptor 4 (TLR4) and its signaling adaptor MyD88 during CNS C. koseri infection have not yet been examined, which is important since recent evidence indicates that innate immune responses are tailored towards specific pathogen classes. Here TLR4 WT (C3H/FeJ) and TLR4 mutant (C3H/HeJ) mice as well as MyD88 KO animals were infected intracerebrally with live C. koseri, resulting in meningitis and ventriculitis with accompanying brain abscess formation. MyD88 KO mice were exquisitely sensitive to C. koseri, demonstrating enhanced mortality rates and significantly elevated bacterial burdens compared to WT animals. Interestingly, although early proinflammatory mediator release (i.e. 12 h) was MyD88-dependent, a role for MyD88-independent signaling was evident at 24 h, revealing a compensatory response to CNS C. koseri infection. In contrast, TLR4 did not significantly impact bacterial burdens or proinflammatory mediator production in response to C. koseri. Similar findings were obtained with primary astrocytes, where MyD88-dependent pathways were essential for chemokine release in response to intact C. koseri, whereas TLR4 was dispensable; implicating the involvement of alternative TLRs since highly enriched astrocytes did not produce IL-1 upon bacterial exposure, which also signals via MyD88. Collectively, these findings demonstrate the importance of MyD88-dependent mechanisms in eliciting maximal proinflammatory responses, astrocyte activation, and bacterial containment during CNS C. koseri infection, as well as a late-phase MyD88-independent signaling pathway for cytokine/chemokine production.
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