IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis
IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis
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DOI：
10.4049/jimmunol.0803039
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发表时间：
2009-06-15
影响因子：
4.4
通讯作者：
Ryffel, Bernhard
中科院分区：
文献类型：
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作者：
Freitas, Andressa;Alves-Filho, Jose C.;Ryffel, Bernhard
脓毒症是由于宿主无法局部控制感染而引起的全身性炎症反应。以前，我们证明，在严重脓毒症有一个显着的中性粒细胞迁移到感染部位，这有助于传播感染，导致高死亡率的失败。IL-17在中性粒细胞募集中起重要作用。在此，我们研究了IL-17 R信号转导在盲肠结扎穿孔（CLP）诱导的多微生物脓毒症中的作用。据观察，与C57 BL/6同窝出生的小鼠相比，IL-17 R缺陷型小鼠（经历CLP诱导的非严重脓毒症）显示出减少的中性粒细胞募集到腹膜腔中、感染扩散和增加的全身炎症反应。结果，小鼠的死亡率增加。在体内和体外证实了IL-17诱导中性粒细胞迁移的能力。除了其在中性粒细胞募集到感染病灶中的作用外，IL-17还通过依赖于NO的机制增强了迁移中性粒细胞的杀微生物活性。因此，IL-17在多微生物脓毒症期间的宿主保护中起着关键作用。免疫学杂志，2009，182：7846-7854.
Sepsis is a systemic inflammatory response resulting from the inability of the host to contain the infection locally. Previously, we demonstrated that during severe sepsis there is a marked failure of neutrophil migration to the infection site, which contributes to dissemination of infection, resulting in high mortality. IL-17 plays an important role in neutrophil recruitment. Herein, we investigated the role of IL-17R signaling in polymicrobial sepsis induced by cecal ligation and puncture (CLP). It was observed that IL-17R-deficient mice, subjected to CLP-induced non-severe sepsis, show reduced neutrophil recruitment into the peritoneal cavity, spread of infection, and increased systemic inflammatory response as compared with C57BL/6 littermates. As a consequence, the mice showed an increased mortality rate. The ability of IL-17 to induce neutrophil migration was demonstrated in vivo and in vitro. Beside its role in neutrophil recruitment to the infection focus, IL-17 enhanced the microbicidal activity of the migrating neutrophils by a mechanism dependent on NO. Therefore, IL-17 plays a critical role in host protection during polymicrobial sepsis. The Journal of Immunology, 2009, 182: 7846-7854.