Griffith Health Institute, School of Public Health, Griffith University, Logan Campus, Meadowbrook, Queensland 4131, Australia.
Vaccine. 2011 Sep 2;29(38):6464-71. doi: 10.1016/j.vaccine.2011.07.041. Epub 2011 Jul 23.
Vaccines that protect against intracellular infections such as malaria, Leishmania and Chlamydia require strong cellular responses based on CD4(+) T cells and CD8(+) T cells in addition to antibodies. Such cell-mediated responses can be potentiated with adjuvants. However, very few adjuvants have been licensed for use in humans; thus there is an urgent need for the discovery of new non-toxic adjuvants in order to produce more efficacious vaccines. Until recently, the mechanisms of how adjuvants worked remained largely unknown, but, it is becoming clearer that many function via host germline-encoded pattern recognition receptors (PRRs) expressed by most immune and non-immune cells. Most PRRs sense infection and transmit a series of signals that ultimately lead to the development of immunity. PRR mediated signalling can be harnessed to search for new vaccine adjuvants. Dendritic cells (DCs) express many PRRs and are remarkably effective at directing T cell immunity. Natural products (NPs) have been the basis of many drugs and are a rich source of immune activators and/or regulators of the immune response. Here we review PRRs in the context of NPs and propose the use of DCs as biological probes to help identify novel immune type molecules and adjuvants within collections of NPs.
预防疟疾、利什曼病和衣原体等细胞内感染的疫苗除了需要抗体外，还需要基于 CD4(+)T 细胞和 CD8(+)T 细胞的强烈细胞反应。此类细胞介导的反应可以通过佐剂增强。然而，仅有极少数佐剂被许可用于人类；因此，迫切需要发现新的无毒佐剂，以生产更有效的疫苗。直到最近，佐剂的作用机制在很大程度上仍不为人知，但越来越清楚的是，许多佐剂通过宿主种系编码的模式识别受体（PRR）发挥作用，这些受体由大多数免疫和非免疫细胞表达。大多数 PRR 感知感染并传递一系列信号，最终导致免疫的发展。PRR 介导的信号可以被利用来寻找新的疫苗佐剂。树突状细胞（DCs）表达许多 PRR，并且在指导 T 细胞免疫方面非常有效。天然产物（NPs）是许多药物的基础，也是免疫激活剂和/或免疫反应调节剂的丰富来源。在这里，我们将在 NPs 的背景下讨论 PRR，并提出使用 DC 作为生物探针来帮助鉴定 NPs 中新型免疫类型分子和佐剂。
