Variability of the Dendritic Cell Response Triggered by Different Serotypes of Aggregatibacter actinomycetemcomitans or Porphyromonas gingivalis Is Toll-Like Receptor 2 (TLR2) or TLR4 Dependent
Variability of the Dendritic Cell Response Triggered by Different Serotypes of Aggregatibacter actinomycetemcomitans or Porphyromonas gingivalis Is Toll-Like Receptor 2 (TLR2) or TLR4 Dependent
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DOI：
10.1902/jop.2014.140326
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发表时间：
2015-01-01
影响因子：
4.3
通讯作者：
Vernal, Rolando
中科院分区：
文献类型：
--
作者：
Diaz-Zuniga, Jaime;Monasterio, Gustavo;Vernal, Rolando
背景：不同血清型的放线聚集菌和牙龈卟啉单胞菌已被证明可诱导不同的树突状细胞（DC）反应。本研究调查了用不同血清型的放线放线菌或牙龈卟啉单胞菌刺激的 DC 产生的细胞因子和 CC 趋化因子受体 (CCR) 是否依赖于 Toll 样受体 2 (TLR2) 和/或 TLR4。 方法：从健康个体中获得树突状细胞，并用不同的放线放线菌或牙龈卟啉单胞菌以 10(2) 的感染复数 (MOI) 进行引发。在存在或不存在抗 TLR2 或抗 TLR4 阻断抗体的情况下检测牙龈卟啉单胞菌血清型。通过流式细胞术、实时逆转录聚合酶链反应和酶联免疫吸附测定对 TLR2 和 TLR4 表达、CCR5 和 CCR6 表达以及白细胞介素 (IL)-1 β、IL-10、IL-12 和 IL-23 表达和分泌进行定量。与用其他血清型刺激的 DC 相比，在 gingivalis 中分别检测到更高水平的 TLR2 或 TLR4。同样，与其他血清型 B 或血清型 K1 引发的 DC 相比，在血清型 b 或血清型 K1 引发的 DC 中检测到更高水平的细胞因子和 CCR，并且这些增加的水平与 TLR2 或 TLR4 的水平呈正相关。当使用特异性抗 TLR2 单克隆抗体阻断 TLR2 信号传导时，血清型 b 诱导的细胞因子和 CCR 表达受到抑制；当 TLR4 信号传导被阻断时，血清型 K1 诱导的反应受到抑制。结论：这些结果表明，在用不同血清型伴放线菌或牙龈卟啉单胞菌刺激的 DC 中检测到的细胞因子分泌和 CCR 表达的变异性分别是 TLR2 或 TLR4 依赖性的。
Background: Different serotypes of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis have been shown to induce differential dendritic cell (DC) responses. This study investigates whether cytokine and CC-chemokine receptor (CCR) production by DCs stimulated with different serotypes of A. actinomycetemcomitans or P. gingivalis is Toll-like receptor 2 (TLR2) and/ or TLR4 dependent.Methods: DCs were obtained from healthy individuals and primed at a multiplicity of infection (MOI) of 10(2) with different A. actinomycetemcomitans or P. gingivalis serotypes in the presence or absence of anti-TLR2 or anti-TLR4 blocking antibodies. TLR2 and TLR4 expression, CCR5 and CCR6 expression, and interleukin (IL)-1 beta, IL-10, IL-12, and IL-23 expression and secretion were quantified by flow cytometry, real-time reverse-transcription polymerase chain reaction, and enzyme-linked immunosorbent assay.Results: When DCs were stimulated with serotype b of A. actinomycetemcomitans or serotype K1 of P. gingivalis, higher levels of TLR2 or TLR4, respectively, were detected compared to DCs stimulated with the other serotypes. Similarly, higher levels of cytokines and CCRs were detected in serotype b-or serotype K1-primed DCs compared to the others, and these increased levels positively correlated with levels of TLR2 or TLR4. When TLR2 signaling was blocked using a specific anti-TLR2 monoclonal antibody, serotype b-induced cytokine and CCR expression was inhibited; when TLR4 signaling was blocked, serotype K1-induced response was inhibited.Conclusions: These results demonstrate that the variability of secretion of cytokines and expression of CCRs detected in DCs stimulated with different serotypes of A. actinomycetemcomitans or P. gingivalis is TLR2 or TLR4 dependent, respectively.