The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury.
The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury.
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DOI：
10.3389/fimmu.2023.1239683
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发表时间：
2023
影响因子：
7.3
通讯作者：
Hazeldine, Jon
中科院分区：
文献类型：
--
作者：
Horner, Emily;Lord, Janet M.;Hazeldine, Jon
与医院获得性感染的发展相关，重大创伤性损伤导致立即和持续的全身免疫抑制状态，但其潜在机制尚不清楚。损伤相关分子模式（DAMP）是在损伤后数分钟、数天和数周内在循环中检测到的，是蛋白质、脂质和DNA的异质性集合，以引发全身炎症反应综合征而闻名。提示在创伤后免疫应答中有额外的免疫调节作用，数据显示DAMP是创伤后免疫抑制的潜在介质。讨论在体外，在体内和离体研究的结果，本综述的目的是总结新出现的免疫耐受性的细胞质，核和神经源性DAMPs的属性。中性粒细胞抗微生物活性的直接抑制，单核细胞和巨噬细胞中内毒素耐受性的诱导，以及髓源性抑制细胞和调节性T细胞的募集、活化和扩增是迄今为止分配给DAMP的一些免疫抑制特性的实例。至关重要的是，随着研究确定DAMP促进免疫抑制的分子机制，已经提出了预防和/或逆转DAMP诱导的免疫抑制的治疗策略。目前正在考虑的方法包括使用合成聚合物或递送血浆蛋白，以抑制循环DAMP，或用DAMP受体拮抗剂治疗严重损伤的患者。然而，由于DAMP与病原体相关分子模式共享信号传导途径，并且促炎反应对于组织再生至关重要，因此需要仔细考虑这些方法，以确保调节DAMP水平和/或其与免疫细胞的相互作用不会对抗微生物防御以及组织修复和伤口愈合的生理反应产生负面影响。
Associated with the development of hospital-acquired infections, major traumatic injury results in an immediate and persistent state of systemic immunosuppression, yet the underlying mechanisms are poorly understood. Detected in the circulation in the minutes, days and weeks following injury, damage associated molecular patterns (DAMPs) are a heterogeneous collection of proteins, lipids and DNA renowned for initiating the systemic inflammatory response syndrome. Suggesting additional immunomodulatory roles in the post-trauma immune response, data are emerging implicating DAMPs as potential mediators of post-trauma immune suppression. Discussing the results of in vitro, in vivo and ex vivo studies, the purpose of this review is to summarise the emerging immune tolerising properties of cytosolic, nuclear and mitochondrial-derived DAMPs. Direct inhibition of neutrophil antimicrobial activities, the induction of endotoxin tolerance in monocytes and macrophages, and the recruitment, activation and expansion of myeloid derived suppressor cells and regulatory T cells are examples of some of the immune suppressive properties assigned to DAMPs so far. Crucially, with studies identifying the molecular mechanisms by which DAMPs promote immune suppression, therapeutic strategies that prevent and/or reverse DAMP-induced immunosuppression have been proposed. Approaches currently under consideration include the use of synthetic polymers, or the delivery of plasma proteins, to scavenge circulating DAMPs, or to treat critically-injured patients with antagonists of DAMP receptors. However, as DAMPs share signalling pathways with pathogen associated molecular patterns, and pro-inflammatory responses are essential for tissue regeneration, these approaches need to be carefully considered in order to ensure that modulating DAMP levels and/or their interaction with immune cells does not negatively impact upon anti-microbial defence and the physiological responses of tissue repair and wound healing.
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DOI：
10.1097/shk.0000000000001969
发表时间：
2022-09-01
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
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通讯作者：
Wong, Hector R.
影响因子：
5.5
作者：
Aneja, Rajesh K.;Tsung, Allan;Fink, Mitchell P.
通讯作者：
Fink, Mitchell P.
影响因子：
4.8
作者：
Anderson, RE;Hansson, LO;Settergren, G
通讯作者：
Settergren, G
DOI：
10.1016/j.injury.2020.03.009
发表时间：
2020-04-01
影响因子：
2.5
作者：
Cahill, Laura A.;Guo, Fei;Lederer, James A.
通讯作者：
Lederer, James A.