Differential Activation of Dendritic Cells by Toll‐like Receptor Agonists Isolated from the Gram‐positive Vaccine Vector Streptococcus gordonii
Differential Activation of Dendritic Cells by Toll‐like Receptor Agonists Isolated from the Gram‐positive Vaccine Vector Streptococcus gordonii
复制标题
从革兰氏阳性疫苗载体戈登链球菌中分离出的 Toll 样受体激动剂对树突状细胞的差异激活
DOI：
10.1111/j.1365-3083.2009.02232.x
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发表时间：
2009
影响因子：
3.7
通讯作者：
Song F Lee
中科院分区：
文献类型：
--
作者：
M. Mayer;C. M. Phillips;R. Townsend;S. Halperin;Song F Lee
口腔粘膜细菌戈登链球菌作为候选的活粘膜疫苗递送载体已经引起了人们的兴趣。S. gordonii已经显示能够以导致抗原呈递免疫细胞活化和成熟的方式活化抗原呈递免疫细胞，然而S.戈登二世这样做是不为人知的。本工作的目的是研究S. gordonii在诱导小鼠树突状细胞（DC）活化和成熟中的作用。从沙门氏菌中提取脂磷壁酸（LTA）、脂蛋白（LP）、肽聚糖（PGN）和DNA。gordonii，并用于刺激鼠DC。分别通过酶联免疫吸附测定和流式细胞术定量响应于细菌组分的细胞因子产生和DC表面标志物上调。将结果与从MyD 88、TRIF [含有TIR（Toll/白细胞介素-1受体）结构域的衔接子诱导的干扰素-β]或toll样受体-2（TLR-2）敲除小鼠衍生的DC获得的数据进行对比。四个S。发现戈登氏菌的细菌组分通过鼠DC差异性地诱导细胞因子的产生和表面标志物的上调。两种全S. gordonii细胞和四种细菌组分在不存在MyD 88的情况下被消除，但在不存在TRIF的情况下没有。LTA、LP和PGN，而DNA和全S. gordonii需要TLR-2来诱导DC反应。结果表明，S.戈登氏菌主要通过MyD 88依赖性和TRIF非依赖性途径激活DC。这种激活可归因于S.戈登氏菌细胞
The oral commensal bacterium Streptococcus gordonii has been gathering interest as a candidate live mucosal vaccine delivery vector. S. gordonii has been shown to be capable of activating antigen presenting immune cells in a manner which leads to their activation and maturation, yet the mechanism used by S. gordonii to do so is poorly understood. The aim of this work was to investigate the immunostimulatory components of S. gordonii in inducing murine dendritic cell (DC) activation and maturation. Lipoteichoic acid (LTA), lipoprotein (LP), peptidoglycan (PGN), and DNA were isolated from S. gordonii, and used to stimulate murine DC. Cytokine production and DC surface marker upregulation in response to the bacterial components was quantified by enzyme‐linked immunosorbent assay and flow cytometry respectively. The results were contrasted against data obtained from DC derived from MyD88, TRIF [TIR(Toll/Interleukin‐1 Receptor)‐domain‐containing adapter‐inducing interferon‐beta] or toll‐like receptor‐2 (TLR‐2) knockout mice. The four S. gordonii bacterial components were found to differentially induce cytokine production and surface marker upregulation by murine DC. Activation of DC by both whole S. gordonii cells and the four bacterial components was abrogated in the absence of MyD88, but not in the absence of TRIF. LTA, LP and PGN, but not DNA and whole S. gordonii, required TLR‐2 to induce a DC response. The results collectively indicate that S. gordonii activates DC predominantly through a MyD88‐dependent and TRIF‐independent pathway. This activation can be attributed to multiple immunostimulatory components present within S. gordonii bacterial cells.