Requirement of TLR4 and CD14 in dendritic cell activation by Hemagglutinin B from Porphyromonas gingivalis.
Requirement of TLR4 and CD14 in dendritic cell activation by Hemagglutinin B from Porphyromonas gingivalis.
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DOI：
10.1016/j.molimm.2009.05.022
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发表时间：
2009-08
影响因子：
3.6
通讯作者：
Katz J
中科院分区：
文献类型：
--
作者：
Gaddis DE;Michalek SM;Katz J
牙龈卟啉单胞菌是一种革兰氏阴性厌氧菌，是慢性成人牙周病的致病菌之一。牙龈卟啉单胞菌的潜在毒力因子是血凝素。来自牙龈卟啉单胞菌的重组血凝素B（rHag B）已被证明通过诱导特异性抗体来激活免疫系统，所述特异性抗体保护免受牙龈卟啉单胞菌感染后的实验性牙周骨损失。由于不同的微生物制品可以通过Toll样受体（TLR）刺激树突状细胞（DC），随后导致T细胞活化和抗体产生，因此我们想要研究rHagB对DC的免疫刺激作用以及TLR信号传导在此过程中的作用。使用不含内毒素的rHag B制剂，我们的研究结果表明，用rHag B刺激小鼠骨髓来源的DC导致共刺激分子CD 86和CD 40的上调，p38和ERK MAP激酶的激活，转录因子NF-κB、CREB和IRF-3的产生，以及IL-6、TNF-α、IL-12 p40的产生，以及IL-10和IFN-β的产生（在较小程度上）。该活化过程完全依赖于TLR 4和CD 14。虽然CD 86的上调不依赖于衔接分子MyD 88，但CD 40的上调和最佳细胞因子（IL-6、TNF-α、IL-12 p40、IL-10和IFN-β）的产生需要MyD 88和TRIF分子。这些结果是重要的，因为它们是第一个提供的见解rHagB与DC和TLR的相互作用。这项研究的信息将有助于设计有效的疫苗策略，对慢性成人牙周病。
Porphyromonas gingivalis is a Gram-negative anaerobic bacterium that is one of the causative agents of chronic adult periodontal disease. Among the potential virulence factors of P. gingivalis are the hemagglutinins. Recombinant Hemagglutinin B (rHagB) from P. gingivalis has been shown to activate the immune system by inducing specific antibodies that protect against experimental periodontal bone loss following P. gingivalis infection. Since different microbial products can stimulate dendritic cells (DC) through Toll-like receptors (TLRs), subsequently leading to T cell activation and antibody production, we wanted to investigate the immunostimulatory effect of rHagB on DC and the role of TLR signaling in this process. Using an endotoxin free rHagB preparation, our results show that stimulation of murine bone marrow-derived DC with rHagB leads to upregulation of the costimulatory molecules CD86 and CD40, activation of p38 and ERK MAP kinases, transcription factors NF-κB, CREB and IRF-3 and the production of IL-6, TNF-α, IL-12p40 and to a lesser extent IL-10 and IFN-β. This activation process was absolutely dependent on TLR4 and CD14. While upregulation of CD86 was independent of the adaptor molecule MyD88, CD40 upregulation and optimal cytokine (IL-6, TNF-α, IL-12p40, IL-10 and IFN-β) production required both MyD88 and TRIF molecules. These results are of importance since they are the first to provide insights into the interaction of rHagB with DC and TLRs. The information from this study will aid in the design of effective vaccines strategies against chronic adult periodontal disease.
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