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变形链球菌壁相关蛋白 A 促进 TLR4 诱导的树突状细胞成熟。

Streptococcus mutans wall-associated protein A promotes TLR4-induced dendritic cell maturation.

机构信息

Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai, China.

出版信息

Scand J Immunol. 2014 Aug;80(2):121-6. doi: 10.1111/sji.12194.

Abstract

Dendritic cells orchestrate innate and adaptive immune responses, which are central to establishing efficient responses to vaccination. Wall-associated protein A (WapA) of Streptococcus mutans was previously used as a vaccine in animal studies for immunization against dental caries. However, as a cell surface protein, whether WapA activates innate immune responses and the effects of WapA on DCs remain unclear. In this study, WapA was cloned into the GST fusion vector pEBG, which can be expressed efficiently in mammalian cells. We found that when added before stimulation with LPS, purified WapA-GST protein increased TLR4-induced NF-κB and MAPK signalling pathway activation. Pretreatment with WapA-GST also increased LPS-induced proinflammatory cytokine production by DCs, including IL-12, IL-6 and TNF-α. Furthermore, expression of the DC maturation markers CD80/86, CD40 and MHC II was also increased by WapA pretreatment. These data indicate that WapA is recognized by DCs and promotes DC maturation.

摘要

树突状细胞(DCs)在先天免疫和适应性免疫反应的调控中发挥核心作用,这对于建立有效的疫苗接种反应至关重要。此前,变形链球菌(Streptococcus mutans)的壁相关蛋白 A(WapA)已被用于动物研究中的龋齿免疫接种疫苗。然而,作为一种细胞表面蛋白,WapA 是否能激活先天免疫反应以及 WapA 对 DCs 的影响尚不清楚。在这项研究中,WapA 被克隆到 GST 融合载体 pEBG 中,该载体可以在哺乳动物细胞中高效表达。我们发现,在 LPS 刺激前添加纯化的 WapA-GST 蛋白可增加 TLR4 诱导的 NF-κB 和 MAPK 信号通路的激活。WapA-GST 的预处理还增加了 LPS 诱导的 DC 产生的促炎细胞因子,包括 IL-12、IL-6 和 TNF-α。此外,WapA 预处理还增加了 DC 成熟标志物 CD80/86、CD40 和 MHC II 的表达。这些数据表明,WapA 被 DCs 识别并促进 DC 成熟。

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