Helicobacter pylori immune escape is mediated by dendritic cell-induced Treg skewing and Th17 suppression in mice.
Helicobacter pylori immune escape is mediated by dendritic cell-induced Treg skewing and Th17 suppression in mice.
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DOI：
10.1053/j.gastro.2009.11.043
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发表时间：
2010-03
期刊：
影响因子：
29.4
通讯作者：
Luther J
中科院分区：
文献类型：
--
作者：
Kao JY;Zhang M;Miller MJ;Mills JC;Wang B;Liu M;Eaton KA;Zou W;Berndt BE;Cole TS;Takeuchi T;Owyang SY;Luther J
幽门螺杆菌感染增加胃Treg反应，这可能有助于幽门螺杆菌免疫逃逸。我们假设幽门螺杆菌通过树突状细胞引导Treg倾斜，从而抑制Th 17免疫。采用双光子显微镜对小鼠胃粘膜固有层树突状细胞进行定位。通过细胞因子的产生和T细胞增殖的刺激来分析细菌脉冲的小鼠骨髓来源的树突状细胞对Th 17和Treg应答的诱导。评估VacA、CagA、TGF-β和IL-10对Th 17/Treg平衡的影响。使用抗-CD 25中和抗体以消耗小鼠中的Tclase，确定Tclase对幽门螺杆菌特异性Th 17应答和幽门螺杆菌密度的体内意义。我们发现，粘膜CD 11 c+树突状细胞位于正常胃上皮细胞的表面附近，幽门螺杆菌感染后，它们的数量增加。对树突状细胞与幽门螺杆菌直接相互作用的研究揭示了Treg-偏斜反应。Treg偏斜不依赖于幽门螺杆菌VacA和CagA，而依赖于TGF-β和IL-10。通过过继转移幽门螺杆菌致敏的DC的体内Treg偏斜降低了胃IL-17/Foxp 3 mRNA表达的比率。CD 25 + T淋巴细胞的耗竭导致幽门螺杆菌密度的早期降低，这与增强的外周幽门螺杆菌特异性Th 17应答相关，但与Th 1应答无关。总体而言，我们的研究表明，幽门螺杆菌改变DC极化的Th 17/Treg平衡向Treg偏向的反应，这抑制了幽门螺杆菌特异性Th 17免疫的有效诱导。
Helicobacter pylori infection increases gastric Treg response, which may contribute to H pylori immune escape. We hypothesize that H pylori directs Treg skewing by way of dendritic cells and thus inhibits Th17 immunity. Two-photon microscopy was used to locate dendritic cells in gastric lamina propria of mice. The induction of Th17 and Treg responses by bacteria-pulsed murine bone marrow–derived dendritic cells was analyzed by cytokine production and stimulation of T cell proliferation. The effect of VacA, CagA, TGF-β, and IL-10 on Th17/Treg balance was assessed. The in vivo significance of Tregs on the H pylori–specific Th17 response and H pylori density was determined using anti-CD25 neutralizing antibodies to deplete Tregs in mice. We showed that mucosal CD11c+ dendritic cells are located near the surface of normal gastric epithelium and their number increased after H pylori infection. Study of the direct interaction of dendritic cells with H pylori revealed a Treg-skewed response. The Treg skewing was independent of H pylori VacA and CagA and dependent on TGF-β and IL-10. In vivo Treg skewing by adoptive transfer of H pylori–pulsed DCs reduces the ratio of gastric IL-17/Foxp3 mRNA expressions. The depletion of CD25+ Tregs results in early reduction of H pylori density, which is correlated with enhanced peripheral H pylori–specific Th17, but not Th1, response. Overall, our study indicates that H pylori alters the DC-polarized Th17/Treg balance towards a Treg-biased response, which suppresses the effective induction of H pylori–specific Th17 immunity.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
29.4
作者：
DeLyria ES;Redline RW;Blanchard TG
通讯作者：
Blanchard TG
影响因子：
32.4
作者：
Aoshi, Taiki;Zinselmeyer, Bernd H.;Miller, Mark J.
通讯作者：
Miller, Mark J.
DOI：
10.1016/0950-3528(95)90043-8
发表时间：
1995-09-01
期刊：
BAILLIERES CLINICAL GASTROENTEROLOGY
影响因子：
--
作者：
DIXON, MF
通讯作者：
DIXON, MF
影响因子：
3.1
作者：
Kranzer, K;Eckhardt, A;Schneider-Brachert, W
通讯作者：
Schneider-Brachert, W