Antiviral Immunity, Biotherapy and Vaccine Unit, Infection and Epidemiology Department, Institut Pasteur, Paris, France.
Cell Death Differ. 2012 Jan;19(1):96-106. doi: 10.1038/cdd.2011.134. Epub 2011 Oct 28.
Dendritic cells (DCs) initiate immune responses by transporting antigens and migrating to lymphoid tissues to initiate T-cell responses. DCs are located in the mucosal surfaces that are involved in human immunodeficiency virus (HIV) transmission and they are probably among the earliest targets of HIV-1 infection. DCs have an important role in viral transmission and dissemination, and HIV-1 has evolved different strategies to evade DC antiviral activity. High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein that can act as an alarmin, a danger signal to alert the innate immune system for the initiation of host defense. It is the prototypic damage-associated molecular pattern molecule, and it can be secreted by innate cells, including DCs and natural killer (NK) cells. The fate of DCs is dependent on a cognate interaction with NK cells, which involves HMGB1 expressed at NK-DC synapse. HMGB1 is essential for DC maturation, migration to lymphoid tissues and functional type-1 polarization of naïve T cells. This review highlights the latest advances in our understanding of the impact of HIV on the interactions between HMGB1 and DCs, focusing on the mechanisms of HMGB1-dependent viral dissemination and persistence in DCs, and discussing the consequences on antiviral innate immunity, immune activation and HIV pathogenesis.
树突状细胞 (DCs) 通过运输抗原和迁移到淋巴组织来启动 T 细胞反应，从而引发免疫反应。DCs 位于参与人类免疫缺陷病毒 (HIV) 传播的黏膜表面，它们可能是 HIV-1 感染的最早靶标之一。DCs 在病毒传播和扩散中发挥着重要作用，HIV-1 已经进化出不同的策略来逃避 DC 的抗病毒活性。高迁移率族蛋白 B1 (HMGB1) 是一种与 DNA 结合的核蛋白，可作为警报素发挥作用，即向先天免疫系统发出危险信号，启动宿主防御。它是典型的损伤相关分子模式分子，可由先天细胞（包括 DC 和自然杀伤 (NK) 细胞）分泌。DC 的命运取决于与 NK 细胞的同源相互作用，这涉及到 NK-DC 突触处表达的 HMGB1。HMGB1 对于 DC 的成熟、向淋巴组织的迁移以及初始 T 细胞的功能性 1 型极化是必不可少的。这篇综述强调了我们对 HIV 对 HMGB1 与 DCs 之间相互作用的影响的最新理解进展，重点讨论了 HMGB1 依赖的病毒在 DCs 中传播和持续存在的机制，并讨论了对抗病毒先天免疫、免疫激活和 HIV 发病机制的影响。
