Traumatic Brain Injury and Peripheral Immune Suppression: Primer and Prospectus.
Traumatic Brain Injury and Peripheral Immune Suppression: Primer and Prospectus.
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DOI：
10.3389/fneur.2015.00235
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发表时间：
2015
影响因子：
3.4
通讯作者：
Belli A
中科院分区：
文献类型：
--
作者：
Hazeldine J;Lord JM;Belli A
医院感染是创伤性脑损伤（TBI）患者的常见事件，与死亡风险增加、住院时间延长和神经功能预后不良相关。作为中枢神经系统（CNS）损伤的直接结果而产生的全身性免疫抑制被认为是感染发病率增加的主要原因，最近的研究报告了TBI后免疫系统的先天性和适应性臂的组成和功能的新变化，从而加强了这一观点。然而，我们对TBI诱导的免疫抑制机制的认识充其量是模棱两可的。在这里，在总结了我们目前对TBI对外周免疫的影响的理解和讨论CNS介导的免疫功能调节后，我们提出了一系列新机制在驱动TBI后观察到的免疫抑制中的作用。在TBI诱导的免疫轻瘫的背景下，这些机制以前从未被考虑过，包括CNS驱动的髓源性抑制细胞和抑制性中性粒细胞亚群进入循环，以及从损伤组织释放核和髓源性损伤相关分子模式。此外，为了进一步了解TBI诱导的免疫变化的机制，我们在整个综述中提出了一系列问题，如果得到回答，将解决一些关键问题，例如确定操纵外周免疫功能是否有潜力作为未来的治疗策略，用于治疗和/或预防住院TBI患者的感染。
Nosocomial infections are a common occurrence in patients following traumatic brain injury (TBI) and are associated with an increased risk of mortality, longer length of hospital stay, and poor neurological outcome. Systemic immune suppression arising as a direct result of injury to the central nervous system (CNS) is considered to be primarily responsible for this increased incidence of infection, a view strengthened by recent studies that have reported novel changes in the composition and function of the innate and adaptive arms of the immune system post-TBI. However, our knowledge of the mechanisms that underlie TBI-induced immune suppression is equivocal at best. Here, after summarizing our current understanding of the impact of TBI on peripheral immunity and discussing CNS-mediated regulation of immune function, we propose roles for a series of novel mechanisms in driving the immune suppression that is observed post-TBI. These mechanisms, which have never been considered before in the context of TBI-induced immune paresis, include the CNS-driven emergence into the circulation of myeloid-derived suppressor cells and suppressive neutrophil subsets, and the release from injured tissue of nuclear and mitochondria-derived damage associated molecular patterns. Moreover, in an effort to further our understanding of the mechanisms that underlie TBI-induced changes in immunity, we pose throughout the review a series of questions, which if answered would address a number of key issues, such as establishing whether manipulating peripheral immune function has potential as a future therapeutic strategy by which to treat and/or prevent infections in the hospitalized TBI patient.