Aliberti Julio, Jankovic Dragana, Sher Alan
Department of Immunology, Duke University School of Medicine, Durham, NC, USA.
Immunol Rev. 2004 Oct;201:26-34. doi: 10.1111/j.0105-2896.2004.00179.x.
Because of its intrinsic virulence, Toxoplasma gondii induces a potent interleukin-12 (IL-12)-dependent cell-mediated immune response that shuts down the growth of the replicative tachyzoite stage, thus promoting host survival and successful transmission through predation. At the same time, this response must be tightly controlled to prevent lethality due to cytokine-mediated immunopathology. Evidence accumulated in recent years suggests that dendritic cells (DCs) play a major role in the initiation of IL-12-driven host resistance and that IL-12 synthesis by DCs is carefully regulated to avoid overproduction. In addition, this work has revealed a critical role for DCs in determining the highly polarized T-helper 1 (Th1)-type response triggered by the parasite. In this review, we summarize our current understanding of how DC function is initiated by Toxoplasma and how parasite-primed DCs drive Th1 effector choice. In addition, we discuss recent findings concerning the pathways responsible for endogenous regulation of DC IL-12 production during T. gondii infection.
由于其内在毒性,刚地弓形虫会引发一种强大的、依赖白细胞介素-12(IL-12)的细胞介导免疫反应,该反应会抑制增殖性速殖子阶段的生长,从而促进宿主存活并通过捕食实现成功传播。与此同时,这种反应必须受到严格控制,以防止因细胞因子介导的免疫病理学导致的致死性。近年来积累的证据表明,树突状细胞(DCs)在启动IL-12驱动的宿主抗性中起主要作用,并且DCs合成IL-12受到精细调节以避免过度产生。此外,这项工作揭示了DCs在决定由寄生虫引发的高度极化的辅助性T细胞1(Th1)型反应中的关键作用。在这篇综述中,我们总结了目前对刚地弓形虫如何启动DC功能以及寄生虫致敏的DCs如何驱动Th1效应子选择的理解。此外,我们讨论了关于刚地弓形虫感染期间负责DCs IL-12产生的内源性调节途径的最新发现。