期刊
JOURNAL OF INFECTIOUS DISEASES
卷 217, 期 3, 页码 393-404出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jix279
关键词
endotoxin tolerance; HIF1 alpha; monocytes; PD-L1; sepsis
资金
- Instituto de Salud Carlos III (ISCiii)
- Fondos de Investigacion Sanitarias (FIS)
- FEDER [PI14/01234, PIE15/00065]
- Comunidad de Madrid [PEJ15/BIO/AI-0021]
- [PI13/01512]
Sepsis, among other pathologies, is an endotoxin tolerance (ET)-related disease. On admission, we classified 48 patients with sepsis into 3 subgroups according to the ex vivo response to lipopolysaccharide. This response correlates with the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the ET degree. Moreover, the ET-related classification determines the outcome of these patients. Programmed cell death-ligand 1 (PD-L1) expression on septic monocytes is also linked with ET status. In addition to the regulation of cytokine production, one of the hallmarks of ET that significantly affects patients with sepsis is T-cell proliferation impairment or a poor switch to the adaptive response. PD-L1/programmed cell death-1 (PD-1) blocking and knockdown assays on tolerant monocytes from both patients with sepsis and the in vitro model reverted the impaired adaptive response. Mechanistically, the transcription factor hypoxia-inducible factor-1 alpha (HIF1 alpha) has been translocated into the nucleus and drives PD-L1 expression during ET in human monocytes. This fact, together with patient classification according to the ex vivo lipopolysaccharide response, opens an interesting field of study and potential personalized clinical applications, not only for sepsis but also for all ET-associated pathologies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据