Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Germany.
Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
Eur J Immunol. 2017 Jul;47(7):1181-1187. doi: 10.1002/eji.201746989. Epub 2017 Jun 1.
Toll-like receptors (TLRs) orchestrate immune responses to a wide variety of danger- and pathogen-associated molecular patterns. Compared to the central nervous system (CNS), expression profile and function of TLRs in the human peripheral nervous system (PNS) are ill-defined. We analyzed TLR expression of satellite glial cells (SGCs) and microglia, glial cells predominantly involved in local immune responses in ganglia of the human PNS and normal-appearing white matter (NAWM) of the CNS, respectively. Ex vivo flow cytometry analysis of cell suspensions obtained from human cadaveric trigeminal ganglia (TG) and NAWM showed that both SGCs and microglia expressed TLR1-5, TLR7, and TLR9, although expression levels varied between these cell types. Immunohistochemistry confirmed expression of TLR1-TLR4 and TLR9 by SGCs in situ. Stimulation of TG- and NAWM-derived cell suspensions with ligands of TLR1-TLR6, but not TLR7 and TLR9, induced interleukin 6 (IL-6) secretion. We identified CD45 CD14 SGCs and microglia, but not CD45 leukocytes and CD45 cells as the main source of IL-6 and TNF-α upon stimulation with TLR3 and TLR5 ligands. In conclusion, human TG-resident SGCs express a broad panel of functional TLRs, suggesting their role in initiating and orchestrating inflammation to pathogens in human sensory ganglia.
Toll 样受体 (TLRs) 协调对多种危险和病原体相关分子模式的免疫反应。与中枢神经系统 (CNS) 相比,TLRs 在人类周围神经系统 (PNS) 中的表达谱和功能尚不清楚。我们分析了卫星神经胶质细胞 (SGCs) 和小胶质细胞中 TLR 的表达,这两种细胞分别主要参与神经节中的局部免疫反应和中枢神经系统正常外观的白质 (NAWM)。从人尸体三叉神经节 (TG) 和 NAWM 获得的细胞悬浮液的体外流式细胞术分析表明,SGCs 和小胶质细胞均表达 TLR1-5、TLR7 和 TLR9,尽管这些细胞类型之间的表达水平有所不同。免疫组织化学原位证实了 TLR1-TLR4 和 TLR9 在 SGCs 中的表达。用 TLR1-TLR6 的配体刺激 TG 和 NAWM 衍生的细胞悬浮液,但不刺激 TLR7 和 TLR9 的配体,诱导白细胞介素 6 (IL-6) 的分泌。我们确定了 CD45 CD14 SGCs 和小胶质细胞,而不是 CD45 白细胞和 CD45 细胞,作为 TLR3 和 TLR5 配体刺激后产生 IL-6 和 TNF-α 的主要来源。总之,人 TG 驻留的 SGCs 表达广泛的功能性 TLR,表明它们在启动和协调人类感觉神经节中病原体的炎症反应中发挥作用。