Damage- and pathogen-associated molecular patterns play differential roles in late mortality after critical illness
Damage- and pathogen-associated molecular patterns play differential roles in late mortality after critical illness
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DOI：
10.1172/jci.insight.127925
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发表时间：
2019-08-22
期刊：
影响因子：
8
通讯作者：
Lee, Jaewoo
中科院分区：
文献类型：
--
作者：
Eppensteiner, John;Kwun, Jean;Lee, Jaewoo
多器官衰竭（MOF）是重症监护病房（icu）患者晚期死亡和发病的主要原因。然而，在脓毒症和创伤患者之间，基于病因的潜在免疫紊乱机制存在流行病学差异。我们假设损伤相关分子模式（DAMPs）和病原体相关分子模式（PAMPs）虽然都参与MOF的发展，但对系统性先天免疫紊乱和凝血病理改变的贡献不同。我们发现，DAMPs不仅比对应的PAMPs产生更弱的先天免疫激活，而且诱导更少的TLR信号脱敏，有助于更少的先天免疫细胞死亡，并且比PAMPs传播更强大的全身凝血作用。这种对MOF的差异贡献提供了对危重创伤和败血症患者晚期死亡的影响因素的进一步了解。这些发现将有助于更好地预测有MOF风险的患者，并可能在该疾病过程中提供未来的治疗分子靶点。
Multiple organ failure (MOF) is the leading cause of late mortality and morbidity in patients who are admitted to intensive care units (ICUs). However, there is an epidemiologic discrepancy in the mechanism of underlying immunologic derangement dependent on etiology between sepsis and trauma patients in MOF. We hypothesized that damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), while both involved in the development of MOF, contribute differently to the systemic innate immune derangement and coagulopathic changes. We found that DAMPs not only produce weaker innate immune activation than counterpart PAMPs, but also induce less TLR signal desensitization, contribute to less innate immune cell death, and propagate more robust systemic coagulopathic effects than PAMPs. This differential contribution to MOF provides further insight into the contributing factors to late mortality in critically ill trauma and sepsis patients. These findings will help to better prognosticate patients at risk of MOF and may provide future therapeutic molecular targets in this disease process.