New York University, School of Medicine, Cancer Institute, New York, NY, USA.
Blood. 2010 Nov 11;116(19):3839-52. doi: 10.1182/blood-2010-03-273763. Epub 2010 Aug 6.
Myeloid and plasmacytoid dendritic cells (DCs) are important mediators of both innate and adaptive immunity against pathogens such as HIV. During the course of HIV infection, blood DC numbers fall substantially. In the present study, we sought to determine how early in HIV infection the reduction occurs and whether the remaining DC subsets maintain functional capacity. We find that both myeloid DC and plasmacytoid DC levels decline very early during acute HIV infection. Despite the initial reduction in numbers, those DCs that remain in circulation retain their function and are able to stimulate allogeneic T-cell responses, and up-regulate maturation markers plus produce cytokines/chemokines in response to stimulation with TLR7/8 agonists. Notably, DCs from HIV-infected subjects produced significantly higher levels of cytokines/chemokines in response to stimulation with TLR7/8 agonists than DCs from uninfected controls. Further examination of gene expression profiles indicated in vivo activation, either directly or indirectly, of DCs during HIV infection. Taken together, our data demonstrate that despite the reduction in circulating DC numbers, those that remain in the blood display hyperfunctionality and implicates a possible role for DCs in promoting chronic immune activation.
髓系和浆细胞样树突状细胞（DCs）是固有免疫和适应性免疫对抗 HIV 等病原体的重要介质。在 HIV 感染过程中，血液 DC 数量大量减少。在本研究中，我们试图确定 HIV 感染早期发生的情况，以及剩余的 DC 亚群是否保持功能能力。我们发现，髓系 DC 和浆细胞样 DC 在急性 HIV 感染早期就明显减少。尽管数量最初减少，但循环中的这些 DC 仍保持其功能，能够刺激同种异体 T 细胞反应，并在 TLR7/8 激动剂刺激下上调成熟标志物和产生细胞因子/趋化因子。值得注意的是，与未感染对照组相比，HIV 感染者的 DC 对 TLR7/8 激动剂的刺激产生更高水平的细胞因子/趋化因子。进一步的基因表达谱分析表明，在 HIV 感染期间，DC 受到体内直接或间接的激活。总之，我们的数据表明，尽管循环 DC 数量减少，但血液中剩余的 DC 表现出高功能，提示 DC 可能在促进慢性免疫激活中起作用。
