Klein Klouwenberg Peter, Tan Lydia, Werkman Wendy, van Bleek Grada M, Coenjaerts Frank
Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands.
Crit Rev Immunol. 2009;29(6):531-50. doi: 10.1615/critrevimmunol.v29.i6.40.
Toll-like receptors (TLRs) play a distinct role in battling respiratory syncytial virus (RSV) infections. However, due to a lack of representative animal models and several early controversies, the field is unclear. In this systematic review, we have elucidated conflicting results and outlined important factors that might affect study outcomes. We reviewed studies that used different doses/viral strains, performed virus propagation in different cell lines, or used different mice strains. The following firm conclusions can be drawn: multiple TLRs activate innate immunity upon RSV infection; TLR4 can influence TLR2 expression, suggesting that optimal induction of multiple signaling pathways is required to elicit protective, rather than deleterious innate immune responses following infection; in mice, TLR4, TLR2/-6, and TLR7 have immune-stimulating properties, while TLR3 activation occurs later and appears to downregulate immune responses; in humans, polymorphism studies have demonstrated an important role for TLR4-signaling; and activation of TLR-signaling leads to antiviral cytokine production, such as TNF-a and IFNs. Viral factors may block these pathways, thereby contributing to immune evasion and RSV survival. A better understanding of the complex interplay between TLRs and severe RSV infections might lead to efficient prophylactic and therapeutic treatments, as well as the development of adequate vaccines combined with TLR adjuvants.
Toll样受体（TLRs）在对抗呼吸道合胞病毒（RSV）感染中发挥着独特作用。然而，由于缺乏具有代表性的动物模型以及早期存在的一些争议，该领域尚不明晰。在本系统综述中，我们阐明了相互矛盾的结果，并概述了可能影响研究结果的重要因素。我们回顾了使用不同剂量/病毒株、在不同细胞系中进行病毒繁殖或使用不同小鼠品系的研究。可以得出以下明确结论：多种TLRs在RSV感染时激活先天免疫；TLR4可影响TLR2表达，这表明在感染后引发保护性而非有害的先天免疫反应需要多种信号通路的最佳诱导；在小鼠中，TLR4、TLR2/-6和TLR7具有免疫刺激特性，而TLR3的激活发生较晚且似乎会下调免疫反应；在人类中，多态性研究已证明TLR4信号传导具有重要作用；TLR信号传导的激活会导致抗病毒细胞因子的产生，如肿瘤坏死因子-α和干扰素。病毒因子可能会阻断这些途径，从而促进免疫逃逸和RSV存活。更好地理解TLRs与严重RSV感染之间的复杂相互作用可能会带来有效的预防和治疗方法，以及开发与TLR佐剂联合使用的合适疫苗。
