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首页> 外文期刊>Infection and immunity >Toll-Like Receptor 2 Deficiency Results in Impaired Antibody Responses and Septic Shock during Borrelia hermsii Infection
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Toll-Like Receptor 2 Deficiency Results in Impaired Antibody Responses and Septic Shock during Borrelia hermsii Infection

机译：Toll样受体2缺乏症导致了埃氏疏螺旋体感染期间抗体反应受损和败血性休克。

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Overwhelming bacteremia is a leading cause of death. To understand the mechanisms involved in protective antibody and pathological inflammatory responses during bacteremia, we have been studying the murine model of Borrelia hermsii infection. Toll-like receptor (TLR) signaling plays an important role in generating the rapid anti-B. hermsii antibody responses required for the resolution of bacteremia. Using NF-κB reporter assays, we found that B. hermsii activates TLR2 and TLR9. However, TLR2?/? TLR9?/? mice exhibited an impairment in anti-B. hermsii antibody responses similar to that of TLR2?/? mice. Moreover, the impairment in the antibody responses of TLR2?/? mice or TLR2?/? TLR9?/? mice coincides with an order-of-magnitude-higher bacteremia, and death results from septic shock, as evidenced by a dysregulated systemic cytokine response and characteristic organ pathology. Since TLR2 appears to be the major extracellular sensor stimulated by B. hermsii, we hypothesized that during elevated bacteremia the activation of intracellular sensors of bacteria triggers dysregulated inflammation in TLR2?/? mice. Indeed, blocking the internalization of B. hermsii prevented the induction of inflammatory cytokine responses in TLR2-deficient cells. Furthermore, we found that B. hermsii activates the cytoplasmic sensor nucleotide-binding oligomerization domain 2 (NOD2). Macrophages deficient in both TLR2 and NOD2 have impaired cytokine responses to B. hermsii compared to cells lacking TLR2 alone, and B. hermsii-infected TLR2?/? NOD2?/? mice exhibited improved survival compared to TLR2?/? mice. These data demonstrate that TLR2 is critical for protective immunity and suggest that, during heightened bacteremia, recognition of bacterial components by intracellular sensors can lead to pathological inflammatory responses.
机译：压倒性菌血症是导致死亡的主要原因。为了了解菌血症期间保护性抗体和病理性炎症反应所涉及的机制，我们一直在研究 Borrelia hermsii 感染的小鼠模型。 Toll样受体（TLR）信号传导在快速产生抗B方面起着重要作用。解决细菌血症所需的hermsii抗体。使用NF-κB报告基因检测，我们发现 B。 hermsii 激活TLR2和TLR9。但是，TLR2 ？/？ TLR9 ？/？小鼠在抗 B方面表现出损伤。 hermsii 抗体反应与TLR2 ？/？小鼠相似。此外，TLR2 ？/？小鼠或TLR2 ？/？ TLR9 ？/？小鼠的抗体反应中的损伤与以下顺序一致：高水平的菌血症和死亡是由败血性休克引起的，全身系统细胞因子反应异常和器官病理特征证明了这一点。由于TLR2似乎是 B刺激的主要细胞外传感器。 Hermsii ，我们假设在菌血症升高期间，细菌细胞内传感器的激活会触发TLR2 ？/？小鼠炎症失调。确实，阻止了 B的内部化。 hermsii 阻止了TLR2缺陷细胞中炎性细胞因子的诱导。此外，我们发现 B。 hermsii 激活细胞质传感器核苷酸结合寡聚域2（NOD2）。 TLR2和NOD2均缺乏的巨噬细胞损害了对 B的细胞因子反应。 Hermsii 与仅缺少TLR2和 B的细胞相比。与TLR2 ？/？小鼠相比，感染hermsii 的TLR2 ？/？ NOD2 ？/？小鼠的存活率有所提高。这些数据表明TLR2对于保护性免疫至关重要，并表明在菌血症加剧期间，细胞内传感器识别细菌成分可导致病理性炎症反应。

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