Pflieger Fabian Johannes, Hernandez Jessica, Schweighöfer Hanna, Herden Christiane, Rosengarten Bernhard, Rummel Christoph
Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, Giessen, Germany.
Institute of Veterinary Pathology, Justus Liebig University Giessen, Giessen, Germany.
Temperature (Austin). 2018 Nov 1;5(4):296-307. doi: 10.1080/23328940.2018.1538598. eCollection 2018.
Immune-to-brain communication has been studied in a variety of experimental models. Crucial insights into signalling and mechanisms were previously revealed in studies investigating fever induction pathways. The scientific community has primarily focused on neuronal and humoral pathways in the manifestation of this response. Emerging evidence has now shown that immune-to-brain signalling via immune cells is pivotal for normal brain function and brain pathology. The present manuscript aims to provide a brief overview on the current understanding of how immune cells signal to the brain. Insights are summarized on the potential physiological significance of some immune cells signalling from the periphery to the brain. A particular focus is laid on the role of neutrophil granulocytes. As such, IL-1β expressing neutrophil granulocytes have been shown to transfer inflammatory information to the brain and contribute to prolonged behavioural changes due to septic encephalopathy in rats during severe systemic inflammation induced by the bacterial component and TLR4 agonist lipopolysaccharide. Modulation of immune cell recruitment to the brain is discussed by various confounding factors including sleep, exercise, the nutritional status e.g. obesity, leptin and omega 3 fatty acids, and psychological or inflammatory stressors. The physiological significance of immune cell mediated communication between the immune system and the brain is highlighted by the fact that systemic inflammatory insults can exacerbate ongoing brain pathologies via immune cell trafficking. New insights into mechanisms and mediators of immune cell mediated immune-to-brain communication are important for the development of new therapeutic strategies and the better understanding of existing ones. : ACTH: adrenocorticotropic hormone; BBB: blood-brain barrier; BBI: blood-brain interface; CD: cluster of differentiation; CINC: cytokine-induced neutrophil chemoattractant; CRH: corticotropin releasing hormone; CVOs: circumventricular organs; CXCR: chemokine receptor; DAPI: 40:6-diamidino-2-phenylindole dilactate; DHA: docosahexaenoid acid; ICAM: intracellular adhesion molecule; IL: interleukin; i.p.: intraperitoneal; i.v.: intravenous; KC: keratinocytes-derived chemokine; LPS: lipopolysaccharide; MIP: macrophage inflammatory protein; MS: multiple sclerosis; NFκB: nuclear factor kappa B; NF-IL6: nuclear factor IL-6; PCTR: protectin conjugates in tissue regeneration; PG: prostaglandin; p.i.: post injection; PVN: paraventricular nucleus; ra: receptor antagonist; STAT3: signal transducer and activator of transcription 3; TIMP: tissue inhibitors of metalloproteinases; TLR: toll-like receptor; TNFα: tumor necrosis factor alpha.
免疫与大脑之间的通讯已在多种实验模型中得到研究。此前，在研究发热诱导途径的实验中，已揭示了有关信号传导和机制的关键见解。科学界主要关注这种反应表现中的神经元和体液途径。现在，新出现的证据表明，免疫细胞介导的免疫与大脑之间的信号传导对于正常脑功能和脑部病理状态至关重要。本手稿旨在简要概述目前对免疫细胞如何向大脑发出信号的理解。总结了一些免疫细胞从外周向大脑发出信号的潜在生理意义的见解。特别关注中性粒细胞的作用。例如，已证明表达白细胞介素 -1β 的中性粒细胞可将炎症信息传递至大脑，并在细菌成分和 Toll 样受体 4 激动剂脂多糖诱导的严重全身炎症期间，导致大鼠因败血症性脑病而出现行为改变持续时间延长。讨论了包括睡眠、运动、营养状况（如肥胖、瘦素和ω-3 脂肪酸）以及心理或炎症应激源等各种混杂因素对免疫细胞向大脑募集的调节作用。全身炎症损伤可通过免疫细胞运输加剧正在进行的脑部病理状态，这一事实凸显了免疫细胞介导的免疫系统与大脑之间通讯的生理意义。免疫细胞介导的免疫与大脑通讯的机制和介质的新见解对于开发新的治疗策略以及更好地理解现有策略非常重要。：促肾上腺皮质激素；血脑屏障；血脑界面；分化簇；细胞因子诱导的中性粒细胞趋化因子；促肾上腺皮质激素释放激素；室周器官；趋化因子受体；4',6-二脒基-2-苯基吲哚二盐酸盐；二十二碳六烯酸；细胞间黏附分子；白细胞介素；腹腔内；静脉内；角质形成细胞衍生的趋化因子；脂多糖；巨噬细胞炎性蛋白；多发性硬化症；核因子κB；核因子白细胞介素-6；组织再生中的保护素缀合物；前列腺素；注射后；室旁核；受体拮抗剂；信号转导和转录激活因子 3；金属蛋白酶组织抑制剂；Toll 样受体；肿瘤坏死因子α
