Department of Microbiology and Immunology, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA 19102, USA.
Viruses. 2012 May;4(5):901-23. doi: 10.3390/v4050901. Epub 2012 May 24.
Toll-like Receptors (TLRs) sense viral infections and induce production of type I interferons (IFNs), other cytokines, and chemokines. Viral recognition by TLRs and other pattern recognition receptors (PRRs) has been proven to be cell-type specific. Triggering of TLRs with selected ligands can be beneficial against some viral infections. Macrophages are antigen-presenting cells that express TLRs and have a key role in the innate and adaptive immunity against viruses. Coronaviruses (CoVs) are single-stranded, positive-sense RNA viruses that cause acute and chronic infections and can productively infect macrophages. Investigation of the interplay between CoVs and PRRs is in its infancy. We assessed the effect of triggering TLR2, TLR3, TLR4, and TLR7 with selected ligands on the susceptibility of the J774A.1 macrophage cell line to infection with murine coronavirus (mouse hepatitis virus, [MHV]). Stimulation of TLR2, TLR4, or TLR7 did not affect MHV production. In contrast, pre-stimulation of TLR3 with polyinosinic-polycytidylic acid (poly I:C) hindered MHV infection through induction of IFN-β in macrophages. We demonstrate that activation of TLR3 with the synthetic ligand poly I:C mediates antiviral immunity that diminishes (MHV-A59) or suppresses (MHV-JHM, MHV-3) virus production in macrophages.
Toll 样受体 (TLRs) 可识别病毒感染并诱导 I 型干扰素 (IFNs)、其他细胞因子和趋化因子的产生。TLRs 和其他模式识别受体 (PRRs) 对病毒的识别已被证明具有细胞类型特异性。用选定的配体触发 TLR 可以对某些病毒感染有益。巨噬细胞是表达 TLR 的抗原呈递细胞，在针对病毒的先天和适应性免疫中发挥关键作用。冠状病毒 (CoVs) 是单链、正链 RNA 病毒，可引起急性和慢性感染，并能有效地感染巨噬细胞。对 CoV 和 PRRs 相互作用的研究仍处于起步阶段。我们评估了用选定的配体触发 TLR2、TLR3、TLR4 和 TLR7 对 J774A.1 巨噬细胞系感染鼠冠状病毒 (小鼠肝炎病毒，[MHV]) 的敏感性的影响。TLR2、TLR4 或 TLR7 的刺激均未影响 MHV 的产生。相比之下，用多聚肌苷酸-多聚胞苷酸 (poly I:C) 预先刺激 TLR3 通过诱导巨噬细胞中的 IFN-β 来阻碍 MHV 感染。我们证明，用合成配体 poly I:C 激活 TLR3 可介导抗病毒免疫，从而减少 (MHV-A59) 或抑制 (MHV-JHM、MHV-3) 巨噬细胞中的病毒产生。
