Piguet Vincent, Blauvelt Andrew
Department of Dermatology, University Hospital of Geneva, Switzerland; Dermatology Branch, National Cancer Institute, Bethesda, Maryland , USA.
J Invest Dermatol. 2002 Aug;119(2):365-9. doi: 10.1046/j.1523-1747.2002.01840.x.
During sexual transmission of HIV, virus crosses mucosal epithelium and eventually reaches lymphoid tissue where it establishes a permanent infection. Evidence has accumulated that infection of Langerhans cells, which are resident dendritic cells in pluristratified epithelia, plays a crucial role in the early events of HIV transmission. HIV infection of Langerhans cells is regulated by surface expression of CD4 and CCR5. Thus, topical microbicides that interfere with HIV infection of Langerhans cells represent an attractive strategy for blocking sexual transmission of virus. Capture and uptake of HIV virions is another major pathway by which HIV interacts with dendritic cells. By contrast, this process is mediated by a newly described C-type lectin, DC-SIGN. It is well established that HIV-exposed dendritic cells transmit virus efficiently to cocultured T cells. Indeed, dendritic cell-T cell interaction, critical in the generation of immune responses, is a rich microenvironment for HIV replication both in vitro and in vivo. Dendritic cells that have captured virus via DC-SIGN, and not HIV-infected dendritic cells, probably facilitate most infection of T cells in chronically infected individuals. Therefore, blocking DC-SIGN-mediated capture of HIV represents a potential therapeutic antiviral strategy for HIV disease. Lastly, dendritic cells have been targeted both ex vivo and in vivo to initiate and enhance HIV-specific immunity. Although these approaches are promising for both therapeutic and prophylactic vaccines, much additional work is needed in order to optimize dendritic-cell-based immunization strategies.
在HIV的性传播过程中，病毒穿过黏膜上皮，最终到达淋巴组织并在那里建立持续感染。越来越多的证据表明，朗格汉斯细胞（复层上皮中的常驻树突状细胞）的感染在HIV传播的早期事件中起着关键作用。朗格汉斯细胞的HIV感染受CD4和CCR5的表面表达调控。因此，干扰朗格汉斯细胞HIV感染的局部杀菌剂是阻断病毒性传播的一种有吸引力的策略。HIV病毒粒子的捕获和摄取是HIV与树突状细胞相互作用的另一条主要途径。相比之下，这个过程由一种新描述的C型凝集素DC-SIGN介导。众所周知，接触过HIV的树突状细胞能有效地将病毒传递给共培养的T细胞。实际上，树突状细胞与T细胞的相互作用在免疫反应的产生中至关重要，在体外和体内都是HIV复制的丰富微环境。通过DC-SIGN捕获病毒的树突状细胞，而非被HIV感染的树突状细胞，可能在慢性感染个体中促进了T细胞的大部分感染。因此，阻断DC-SIGN介导的HIV捕获是一种潜在的HIV疾病治疗性抗病毒策略。最后，树突状细胞在体外和体内都已成为启动和增强HIV特异性免疫的靶点。尽管这些方法对治疗性疫苗和预防性疫苗都很有前景，但为了优化基于树突状细胞的免疫策略，还需要做更多的工作。
