Dual protective mechanisms of matrix metalloproteinases 2 and 9 in immune defense against Streptococcus pneumoniae.
Dual protective mechanisms of matrix metalloproteinases 2 and 9 in immune defense against Streptococcus pneumoniae.
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DOI：
10.4049/jimmunol.1003449
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Kheradmand F
中科院分区：
文献类型：
--
作者：
Hong JS;Greenlee KJ;Pitchumani R;Lee SH;Song LZ;Shan M;Chang SH;Park PW;Dong C;Werb Z;Bidani A;Corry DB;Kheradmand F
针对病原细菌入侵的局部有效的先天免疫反应对于宿主的生存至关重要。识别肺防御此类病原体的关键局部先天介质对于全面了解有效宿主防御的机制至关重要。在肺炎链球菌肺部感染的急性模型中，基质金属蛋白酶 (MMP)2 和 MMP9 (Mmp2/9−/−) 的缺乏导致相对于相同条件下治疗的野生型小鼠的生存劣势。感染肺炎链球菌的 Mmp2/9−/− 小鼠将更多的多形核白细胞募集到肺部，但细菌负荷更高。 Mmp2/9−/− 小鼠肺部的 IL-17A、IP-10 和 RANTES 水平显着升高。尽管 MMP2 依赖性裂解部分灭活了 IL-17A，但 MMP9 对于多形核中性粒细胞中有效的细菌吞噬作用和活性氧生成至关重要。这些数据表明 MMP2 和 MMP9 在针对肺炎链球菌感染的早期宿主免疫反应中发挥着关键的非冗余和保护作用。
A localized and effective innate immune response to pathogenic bacterial invasion is central to host survival. Identification of the critical local innate mediators of lung defense against such pathogens is essential for a complete understanding of the mechanism(s) underlying effective host defense. In an acute model of Streptococcus pneumoniae lung infection, deficiency in matrix metalloproteinase (MMP)2 and MMP9 (Mmp2/9−/−) conferred a survival disadvantage relative to wild-type mice treated under the same conditions. S. pneumoniae-infected Mmp2/9−/− mice recruited more polymorphonuclear leukocytes to the lung but had higher bacterial burdens. Mmp2/9−/− mice showed significantly higher levels of IL-17A, IP-10, and RANTES in the lung. Although MMP2-dependent cleavage partially inactivated IL-17A, MMP9 was critical for effective bacterial phagocytosis and reactive oxygen species generation in polymorphonuclear neutrophils. These data demonstrate critical nonredundant and protective roles for MMP2 and MMP9 in the early host immune response against S. pneumoniae infection.
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影响因子：
9
作者：
Kolls, Jay K.
通讯作者：
Kolls, Jay K.
影响因子：
44.1
作者：
Chang, Seon Hee;Dong, Chen
通讯作者：
Dong, Chen
影响因子：
30.5
作者：
Corry, DB;Rishi, K;Kheradmand, F
通讯作者：
Kheradmand, F
影响因子：
64.8
作者：
Houghton, A. McGarry;Hartzell, William O.;Robbins, Clinton S.;Xavier Gomis-Rueth, F.;Shapiro, Steven D.
通讯作者：
Shapiro, Steven D.
影响因子：
4.8
作者：
Corry, DB;Kiss, A;Kheradmand, F
通讯作者：
Kheradmand, F