Immunoglobulin-Like Transcript 5 Inhibits Macrophage-Mediated Bacterial Killing and Antigen Presentation During Sepsis
Immunoglobulin-Like Transcript 5 Inhibits Macrophage-Mediated Bacterial Killing and Antigen Presentation During Sepsis
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免疫球蛋白样转录本 5 抑制脓毒症期间巨噬细胞介导的细菌杀伤和抗原呈递
DOI：
10.1093/infdis/jiz319
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发表时间：
2019-11-15
影响因子：
6.4
通讯作者：
Huang, Xi
中科院分区：
文献类型：
--
作者：
Ming, Siqi;Li, Musheng;Huang, Xi
背景：免疫抑制与脓毒症的死亡率有关。然而，其潜在的机制仍不清楚。方法：在本研究中，我们研究了抑制性受体免疫球蛋白样转录本5（ILT 5）在脓毒症中的作用。我们首先筛选了ILT家族成员的表达，我们发现ILT 5在脓毒症患者的外周血单个核细胞中显著上调，而健康人则相反。结果：小干扰核糖核酸敲低ILT 5可增加THP-1和RAW264.7细胞的细菌杀伤和活性氧产生。此外，ILT 5表达单核细胞/巨噬细胞表现出较低的抗原呈递分子，包括主要组织相容性复合物-II和CD 80的表达。在体外单核/巨噬细胞共培养体系中，ILT 5的阻断促进了Th 1的增殖和CD 4（+）T细胞的分化。此外，在体内实验表明，ILT 5阻断肽预处理改善了脓毒症小鼠的生存和肺病理学。结论：总之，我们的研究确定ILT 5作为免疫抑制调节剂在脓毒症，这可能提供潜在的治疗策略脓毒症。
Background: Immunosuppression contributes to the mortality of sepsis. However, the underlying mechanism remains unclear.Methods: In the present study, we investigated the role of inhibitory receptor immunoglobulin-like transcript 5 (ILT5) in sepsis. We first screened the expression of ILT family members, and we found that ILT5 was dramatically up-regulated in the peripheral blood mononuclear cells from sepsis patients versus healthy donors.Results: Knockdown of ILT5 by small interfering ribonucleic acid increased bacterial killing and reactive oxygen species production in THP-1 and RAW264.7 cells. Moreover, ILT5-expressing monocytes/macrophages exhibited lower expression of antigen-presenting molecules including major histocompatibility complex-II and CD80. In the in vitro coculture system with monocytes/macrophages, blockage of ILT5 facilitated Th1 proliferation and differentiation of CD4(+) T cells. Furthermore, in vivo experiments demonstrated that pretreatment with ILT5 blocking peptide improved the survival and pulmonary pathology of septic mice.Conclusions: Together, our study identified ILT5 as an immunosuppressive regulator during sepsis, which may provide potential therapeutic strategy for sepsis.