Important Role for CC Chemokine Ligand 2-Dependent Lung Mononuclear Phagocyte Recruitment to Inhibit Sepsis in Mice Infected with Streptococcus pneumoniae 1
Important Role for CC Chemokine Ligand 2-Dependent Lung Mononuclear Phagocyte Recruitment to Inhibit Sepsis in Mice Infected with Streptococcus pneumoniae 1
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DOI：
10.4049/jimmunol.0804096
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发表时间：
2009-04
期刊：
影响因子：
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通讯作者：
C. Winter;Wiebke Herbold;R. Maus;F. Länger;D. Briles;J. Paton;T. Welte;U. Maus
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文献类型：
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作者：
C. Winter;Wiebke Herbold;R. Maus;F. Länger;D. Briles;J. Paton;T. Welte;U. Maus
单核细胞趋化因子CCL2在炎症单核细胞响应细菌感染募集到肺部中具有重要作用。肺炎链球菌是社区获得性肺炎中最普遍的病原体，在世界范围内引起显著的发病率和死亡率。在目前的研究中，我们检测了CCL2在肺保护性免疫中对两种S.肺炎克雷伯氏菌表现出不同的毒力谱。野生型小鼠和CCL2敲除（KO）小鼠在感染血清型3 S后24 h内均出现脓毒症。肺炎，并在攻击后第4天死于感染。相反，用血清型19 S.感染肺炎的小鼠没有变得败血症或死于肺炎球菌肺炎，而CCL2 KO小鼠在感染后第2天开始在其肺中显示早期细菌生长和败血症，最终导致与野生型小鼠相比存活率降低约50%。这种表型不是由于KO小鼠中肺中性粒细胞募集受损，而是以肺渗出物巨噬细胞和常规肺树突状细胞的募集显著减少为特征，表明这两种吞噬细胞亚群关键性地调节对小鼠脓毒性疾病进展的保护作用。总之，我们在这里显示了CCL2依赖性肺渗出巨噬细胞和传统树突状细胞募集的不同作用，这对肺保护性免疫抵抗S。肺炎。
The monocyte chemoattractant CCL2 is of major importance in inflammatory monocyte recruitment to the lungs in response to bacterial infection. Streptococcus pneumoniae is the most prevalent pathogen in community-acquired pneumonia causing significant morbidity and mortality worldwide. In the current study, we examined the role of CCL2 in lung-protective immunity against two strains of S. pneumoniae exhibiting different virulence profiles. Both wild-type mice and CCL2 knockout (KO) mice became septic within 24 h of infection with serotype 3 S. pneumoniae and died of infection by day 4 after challenge. In contrast, wild-type mice challenged with serotype 19 S. pneumoniae did not become septic or succumb to pneumococcal pneumonia, whereas CCL2 KO mice showed an early bacterial outgrowth in their lungs and sepsis starting by day 2 after infection, finally resulting in ∼50% decreased survival compared with wild-type mice. This phenotype was not due to impaired lung neutrophil recruitment in the KO mice, but was characterized by a significantly reduced recruitment of lung exudate macrophages and conventional lung dendritic cells, suggesting that these two phagocyte subsets critically regulate protection against septic disease progression in mice. In conclusion, we show here a differential role for CCL2-dependent lung exudate macrophage and conventional dendritic cell recruitment that critically contributes to lung protective immunity against S. pneumoniae.