Deletion of Nlrp3 Augments Survival during Polymicrobial Sepsis by Decreasing Autophagy and Enhancing Phagocytosis.
Deletion of Nlrp3 Augments Survival during Polymicrobial Sepsis by Decreasing Autophagy and Enhancing Phagocytosis.
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通过减少自噬和增强吞噬作用，NLRP3的缺失增强了多数型败血症期间的存活。
DOI：
10.4049/jimmunol.1601745
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发表时间：
2017-02-01
期刊：
影响因子：
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通讯作者：
Jeyaseelan S
中科院分区：
文献类型：
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作者：
Jin L;Batra S;Jeyaseelan S
NLRP 3炎性小体是先天免疫中的关键参与者。中性粒细胞向组织的募集和中性粒细胞的有效功能是细菌清除的关键先天免疫功能。然而，NLRP 3在多微生物败血症中嗜中性粒细胞依赖性细菌清除中的作用尚不清楚。在此，我们评估了NLRP 3在盲肠结扎穿孔（CLP）诱导的多微生物脓毒症中的作用。我们的研究结果显示NLRP 3缺陷（Nlrp 3-/-）和NLRP 3受体处理的野生型（C57 Bl/6）小鼠的死亡保护。Nlrp 3 −/−和NLRP 3受体处理的小鼠均显示出较低的细菌负荷，尽管在中性粒细胞向腹膜的募集方面没有损害。然而，中性粒细胞耗竭废除了对nd NLRP 3缺陷（Nlrp 3 −/−）小鼠响应CLP的死亡的保护。有趣的是，CLP后的Nlrp 3 −/−腹膜细胞（主要是中性粒细胞）表现出自噬减少，吞噬作用增强和清道夫受体（MARCO）和甘露糖结合瘦素（MBL）表达增强。这些发现增强了我们对NLRP 3在调节中性粒细胞中的自噬和吞噬作用中的关键作用的理解，并表明治疗应靶向调节中性粒细胞中的自噬和吞噬作用，以控制CLP诱导的多微生物脓毒症期间组织中的细菌负荷。
NLRP3 inflammasome is a critical player in innate immunity. Neutrophil recruitment to tissues and effective function of neutrophils are critical innate immune function to bacterial clearance. However, the role of NLRP3 in neutrophil-dependent bacterial clearance in polymicrobial sepsis is unclear. Herein, we evaluated the role of NLRP3 in polymicrobial sepsis induced by cecal ligation and puncture (CLP). Our results exhibit protection from death in NLRP3-deficient (Nlrp3−/−) and NLRP3 inhibitor-treated wild-type (C57Bl/6) mice. Both Nlrp3−/− and NLRP3 inhibitor-treated mice displayed lower bacterial load albeit no impairment in neutrophil recruitment to peritoneum. However, neutrophil depletion abrogated protection from death of nd NLRP3-deficient (Nlrp3−/−) mice in response to CLP. Intriguingly, Nlrp3−/− peritoneal cells (primarily neutrophils) following CLP demonstrate decreased autophagy, augmented phagocytosis and enhanced scavenger receptor (MARCO) and mannose binding leptin (MBL) expression. These findings enhance our understanding of the critical role of NLRP3 in modulating autophagy and phagocytosis in neutrophils and suggest that therapies should be targeted to modulate both autophagy and phagocytosis in neutrophils to control bacterial burden in tissues during CLP-induced polymicrobial sepsis.