IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection
IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection
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DOI：
10.1016/j.micinf.2006.10.012
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发表时间：
2007-01-01
影响因子：
5.8
通讯作者：
Chu, Hong Wei
中科院分区：
文献类型：
--
作者：
Wu, Qun;Martin, Richard J.;Chu, Hong Wei
IL-23 诱导活化的 CD4+ T 细胞产生 IL-17，并参与宿主针对许多有荚膜细菌的防御。然而，IL-23/IL-17 轴是否会导致肺炎支原体 (Mp) 诱导的肺部炎症（例如中性粒细胞）尚未得到解决。利用急性呼吸道Mp感染小鼠模型，我们发现感染早期（4小时）肺IL-23p19 mRNA显着上调，肺泡巨噬细胞是Mp诱导IL-23的重要细胞来源。我们进一步表明，Mp 显着增加支气管肺泡灌洗液 (BAL) 中的 IL-17 蛋白水平。体内Mp也显着上调肺脏基因IL-17、IL-17C和IL-17F的表达。研究发现 IL-17 和 IL-17F 主要来源于肺 CD4+ T 细胞，并在体外受 IL-23 刺激后增加。体内单独阻断IL-23p19或与IL-23/IL-12p40联合阻断IL-23p19可导致Mp诱导的IL-17蛋白和IL-17/IL-17F mRNA表达显着降低，并伴有肺中性粒细胞募集、BAL中性粒细胞活性和Mp清除率降低的趋势。然而，IL-23 中和对 Mp 诱导的肺 IL-17C mRNA 表达没有影响。这些结果表明，在急性 Mp 感染中，IL-17/IL-17F 的产生是 IL-23 依赖性的，并有助于中性粒细胞的募集和肺防御感染的活性。 (c) 2006 年 Elsevier Masson SAS。版权所有。
IL-23 induces IL-17 production in activated CD4+ T cells and participates in host defense against many encapsulated bacteria. However, whether the IL-23/IL-17 axis contributes to a Mycoplasma pneumoniae (Mp)-induced lung inflammation (e.g., neutrophils) has not been addressed. Using an acute respiratory Mp infection murine model, we found significantly up-regulated lung IL-23p19 mRNA in the early phase of infection (4 h), and alveolar macrophages were an important cell source of Mp-induced IL-23. We further showed that Mp significantly increased IL-17 protein levels in bronchoalveolar lavage (BAL). Lung gene expression of IL-17, IL-17C and IL-17F was also markedly up-regulated by Mp in vivo. IL-17 and IL-17F were found to be derived mainly from lung CD4+ T cells, and were increased upon IL-23 stimulation in vitro. In vivo blocking of IL-23p19 alone or in combination with IL-23/IL-12p40 resulted in a significant reduction of Mp-induced IL-17 protein and IL-17/IL-17F mRNA expression, which was accompanied by a trend toward reduced lung neutrophil recruitment, BAL neutrophil activity, and Mp clearance. However, IL-23 neutralization had no effect on Mp-induced lung IL-17C mRNA expression. These results demonstrate that IL-17/IL-17F production is IL-23-dependent in an acute Mp infection, and contributes to neutrophil recruitment and activity in the lung defense against the infection. (c) 2006 Elsevier Masson SAS. All rights reserved.