Institute of Neuropathology, University Medical Center, Göttingen, Germany.
J Neuroinflammation. 2013 Jun 5;10:71. doi: 10.1186/1742-2094-10-71.
Toll-Like receptors (TLRs) belong to the family of pattern-recognition receptors with a crucial function of recognising pathogen-associated molecular patterns (PAMPs). Cryptococcal meningitis is a potentially fatal disease with a high mortality and risk of neurological sequelae.
We studied the ability of microglial cells to increase the phagocytosis of cryptococci after stimulation with agonists of TLR1/2, TLR3, TLR4 and TLR9.
Stimulation of murine microglial cells with these TLR agonists for 24 h increased the phagocytosis of encapsulated Cryptococcus neoformans. Stimulation increased the release of TNF-α, CXCL1 (KC), IL-6, IL-10 and MIP-2, which indicated the activation of microglial cells. Unstimulated and TLR agonist-stimulated MyD88-deficient cells showed a reduced ability to phagocytose cryptococci compared to their wild-type counterpart. Intracellular killing of cryptococci was also increased in TLR-stimulated cells compared to unstimulated microglial cells.
Our observation suggests that stimulation of microglial cells by TLR agonists can increase the resistance of the brain against CNS infections caused by Cryptococcus neoformans. This may be of interest when an immunocompromised patient is unable to eliminate Cryptococcus neoformans despite antifungal therapy.
Toll 样受体（TLRs）属于模式识别受体家族，具有识别病原体相关分子模式（PAMPs）的关键功能。隐球菌性脑膜炎是一种潜在致命的疾病，死亡率高，有发生神经后遗症的风险。
我们研究了小胶质细胞在受到 TLR1/2、TLR3、TLR4 和 TLR9 激动剂刺激后增加对隐球菌吞噬作用的能力。
用这些 TLR 激动剂刺激小鼠小胶质细胞 24 小时可增加对荚膜隐球菌新生隐球菌的吞噬作用。刺激增加了 TNF-α、CXCL1（KC）、IL-6、IL-10 和 MIP-2 的释放，表明小胶质细胞被激活。与野生型相比，未受刺激和 TLR 激动剂刺激的 MyD88 缺陷细胞吞噬隐球菌的能力降低。与未受刺激的小胶质细胞相比，TLR 刺激的细胞内隐球菌杀伤能力也增加。
我们的观察表明，TLR 激动剂刺激小胶质细胞可以提高大脑对由新生隐球菌引起的中枢神经系统感染的抵抗力。当免疫功能低下的患者尽管接受抗真菌治疗仍无法清除新生隐球菌时，这可能是有意义的。
