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分枝杆菌感染小鼠的树突状细胞通过分泌白细胞介素-10 和白细胞介素-12 抑制豚草过敏原诱导的已建立的过敏性气道炎症反应。

Dendritic cells from mycobacteria-infected mice inhibits established allergic airway inflammatory responses to ragweed via IL-10- and IL-12-secreting mechanisms.

机构信息

Immune Regulation of Allergy Research Group, Department of Medical Microbiology, Winnipeg, Mantioba, Canada.

出版信息

J Immunol. 2010 Jun 15;184(12):7288-96. doi: 10.4049/jimmunol.0902829. Epub 2010 May 17.

Abstract

Previous studies have demonstrated that Mycobacterium bovis bacillus Calmette-Guerin (BCG) infection can inhibit de novo and established allergen-induced asthma-like responses. The aim of this study was to examine the role of dendritic cells (DCs) in BCG infection-mediated inhibition of established allergy to a common environmental allergen--ragweed. The results showed that adoptive transfer of DCs from BCG-infected mice (DC[BCG]), in contrast to DCs from naive mice (DC[naive]), significantly inhibited established allergic airway eosinophilia and mucus overproduction. The inhibitory effect was correlated with alterations of allergen-driven cytokine and chemokine production as well as VCAM-1 expression in the lung. Flow cytometric analysis showed higher surface expression of CD8alpha and costimulatory markers in DC(BCG) than in DC(naive). Moreover, DC(BCG) produced significantly higher levels of IL-10 and IL-12 and expressed higher levels of TLRs than did DC(naive). Furthermore, blockade of IL-10 or IL-12 significantly reversed the inhibitory effect of DC(BCG) on established allergic airway inflammation and Th2 cytokine responses. These findings suggest that DCs play a crucial role in infection-mediated inhibition of established allergic responses, and IL-10 and IL-12 production by these DCs may be a major mechanism for the inhibition.

摘要

先前的研究已经表明,牛型结核分枝杆菌卡介苗(BCG)感染可以抑制新发生的和已建立的变应原诱导的哮喘样反应。本研究旨在探讨树突状细胞(DC)在 BCG 感染介导的抑制常见环境变应原——豚草变应性中的作用。结果表明,与来自未感染小鼠的 DC(DC[naive])相比,来自 BCG 感染小鼠的 DC(DC[BCG])的过继转移显著抑制了已建立的变应性气道嗜酸性粒细胞增多和粘液过度产生。这种抑制作用与变应原驱动的细胞因子和趋化因子产生以及肺中 VCAM-1 表达的改变有关。流式细胞术分析显示,DC[BCG]表面 CD8α和共刺激标志物的表达高于 DC[naive]。此外,DC[BCG]产生的 IL-10 和 IL-12 水平明显高于 DC[naive],并且表达的 TLRs 水平也高于 DC[naive]。此外,阻断 IL-10 或 IL-12 显著逆转了 DC[BCG]对已建立的变应性气道炎症和 Th2 细胞因子反应的抑制作用。这些发现表明,DC 在感染介导的已建立的变应性反应抑制中发挥关键作用,并且这些 DC 产生的 IL-10 和 IL-12 可能是抑制的主要机制。

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