Butchi Niranjan B, Pourciau Susan, Du Min, Morgan Tim W, Peterson Karin E
Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
J Immunol. 2008 Jun 1;180(11):7604-12. doi: 10.4049/jimmunol.180.11.7604.
Activation of astrocytes and microglia and the production of proinflammatory cytokines and chemokines are often associated with virus infection in the CNS as well as a number of neurological diseases of unknown etiology. These inflammatory responses may be initiated by recognition of pathogen-associated molecular patterns (PAMPs) that stimulate TLRs. TLR7 and TLR8 were identified as eliciting antiviral effects when stimulated by viral ssRNA. In the present study, we examined the potential of TLR7 and/or TLR8 agonists to induce glial activation and neuroinflammation in the CNS by intracerebroventricular inoculation of TLR7 and/or TLR8 agonists in newborn mice. The TLR7 agonist imiquimod induced astrocyte activation and up-regulation of proinflammatory cytokines and chemokines, including IFN-beta, TNF, CCL2, and CXCL10. However, these responses were only of short duration when compared with responses induced by the TLR4 agonist LPS. Interestingly, some of the TLR7 and/or TLR8 agonists differed in their ability to activate glial cells as evidenced by their ability to induce cytokine and chemokine expression both in vivo and in vitro. Thus, TLR7 stimulation can induce neuroinflammatory responses in the brain, but individual TLR7 agonists may differ in their ability to stimulate cells of the CNS.
星形胶质细胞和小胶质细胞的激活以及促炎细胞因子和趋化因子的产生，通常与中枢神经系统中的病毒感染以及一些病因不明的神经疾病有关。这些炎症反应可能由刺激Toll样受体（TLR）的病原体相关分子模式（PAMP）识别引发。TLR7和TLR8被确定在受到病毒单链RNA刺激时会引发抗病毒作用。在本研究中，我们通过向新生小鼠脑室内接种TLR7和/或TLR8激动剂，研究了TLR7和/或TLR8激动剂在中枢神经系统中诱导胶质细胞激活和神经炎症的潜力。TLR7激动剂咪喹莫特诱导星形胶质细胞激活以及促炎细胞因子和趋化因子上调，包括IFN-β、TNF、CCL2和CXCL10。然而，与TLR4激动剂脂多糖（LPS）诱导的反应相比，这些反应持续时间较短。有趣的是，一些TLR7和/或TLR8激动剂在激活胶质细胞的能力上存在差异，这在它们体内和体外诱导细胞因子和趋化因子表达的能力上得到了证明。因此，TLR7刺激可在脑中诱导神经炎症反应，但不同的TLR7激动剂刺激中枢神经系统细胞的能力可能不同。
