IL-27 controls sepsis-induced impairment of lung antibacterial host defence
IL-27 controls sepsis-induced impairment of lung antibacterial host defence
复制标题
IL-27 控制脓毒症引起的肺部抗菌宿主防御损伤
DOI：
10.1136/thoraxjnl-2014-205777
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发表时间：
2014-10-01
期刊：
影响因子：
10
通讯作者：
Yin, Yibing
中科院分区：
文献类型：
--
作者：
Cao, Ju;Xu, Fang;Yin, Yibing
背景白细胞介素27（IL-27）是调节宿主免疫应答的重要细胞因子。然而，其在脓毒症诱导的免疫抑制中的作用仍不清楚。目的利用盲肠结扎穿孔（CLP）诱导的脓毒症小鼠模型，研究白细胞介素27（IL-27）在脓毒症诱导的免疫抑制中的作用。方法将野生型（WT）和IL-27受体（IL-27 R）/WSX-1基因敲除（KO）小鼠分别进行CLP或假手术，然后用铜绿假单胞菌感染小鼠。结果脓毒症患者和脓毒症小鼠IL-27表达上调。在脓毒症和继发性肺内细菌攻击后，与WT小鼠相比，IL-27 R KO小鼠具有更高的存活率和改善的肺和血液细菌清除率，这与早期肺细胞因子/趋化因子产生增加以及增强的中性粒细胞向空气空间的募集有关。IL-27在脓毒症小鼠中的中和作用显著改善了感染铜绿假单胞菌的脓毒症小鼠的肺中细菌的存活和清除，并且直接应用重组IL-27可以增加对铜绿假单胞菌感染的易感性。脓毒症IL-27 R KO小鼠对继发性铜绿假单胞菌感染的抵抗力通过肺泡巨噬细胞（AM）和中性粒细胞的消耗而消除。与WT小鼠相比，脓毒症IL-27 R KO小鼠的AM具有更高的细菌摄取和杀伤能力，增强的细胞因子/趋化因子产生，以及增加的共刺激分子表达，而与WT中性粒细胞相比，脓毒症IL-27 R KO小鼠的中性粒细胞具有增加的细菌杀伤能力和更高的粘附分子Mac-1表达。结论IL-27是脓毒症肺组织抗菌宿主防御功能受损的重要介质。
Background Interleukin 27 (IL-27) is an important cytokine regulating host immune responses. However, its role in sepsis-induced immunosuppression remains unclear. Aim To investigate the role of IL-27 in modulating sepsis-induced immunosuppression using a murine model of caecal ligation and puncture (CLP)-induced sepsis followed by secondary challenge with Pseudomonas aeruginosa. Methods CLP or sham surgery was performed in wild-type (WT) and IL-27 receptor (IL-27R)/WSX-1 knockout (KO) mice, and then mice were infected with intratracheal P aeruginosa. Results IL-27 was upregulated in patients with sepsis and septic mice. Following sepsis and secondary intrapulmonary bacterial challenge, IL-27R KO mice had higher survival rates and improved bacterial clearance from lung and blood compared with WT mice, which was associated with early increased pulmonary cytokine/chemokine production, as well as enhanced neutrophil recruitment to airspaces. Neutralisation of IL-27 in septic mice significantly improved survival and clearance of bacteria from the lungs of septic mice infected with P aeruginosa, and direct application of recombinant IL-27 could increase susceptibility to P aeruginosa infection. The resistance of septic IL-27R KO mice to secondary P aeruginosa infection was abrogated by depletion of alveolar macrophages (AMs) and neutrophils. AMs from septic IL-27R KO mice had higher bacterial uptake and killing capacities, enhanced cytokine/chemokine production, and increased expression of costimulatory molecules compared with those from WT mice, while neutrophils from septic IL-27R KO mice had increased bacterial killing ability and higher expression of adhesion molecule Mac-1 compared with WT neutrophils. Conclusions IL-27 is an important mediator of sepsis-induced impairment of lung antibacterial host defence.