A dominant role for FcγRll in anti body-enhanced dengue virus infection of human mast cells and associated CCL5 release
A dominant role for FcγRll in anti body-enhanced dengue virus infection of human mast cells and associated CCL5 release
复制标题
DOI：
10.1189/jlb.0805441
复制
发表时间：
2006-12-01
影响因子：
5.5
通讯作者：
Anderson, Robert
中科院分区：
文献类型：
--
作者：
Brown, Michael G.;King, Christine A.;Anderson, Robert
登革热病毒是一种主要的蚊媒人类病原体，有四种已知血清型。在登革热病毒感染之前，个体血清中存在抗登革热病毒抗体被认为是严重登革热病毒病的重要危险因素，这是由于 Fe 受体 (FcR) 听觉细胞上抗体依赖性增强现象的结果。除了血液单核细胞外，肥大细胞也容易受到抗体增强的登革热病毒感染，产生许多炎症介质，包括 IL-1、IL-6 和 CCL5。使用人类肥大细胞系 KU812 和 HMC-1 以及人类脐带血源性肥大细胞 (CBMC) 的原代培养物，我们的目的是鉴定抗体增强肥大细胞登革热病毒感染中参与的 FcR，因为 FcR 代表了治疗干预的潜在位点。 CBMC 表达显着水平的 Fc γ RI、Fc γ RII 和 Fc γ RIII，肥大细胞样 HMC-1 和 KU812 细胞主要表达 Fc γ RII。登革热病毒的所有四种血清型均显示出与 KU812 细胞的抗体增强结合。发现在登革热特异性抗体存在的情况下，使用 mAb IV.3 特异性 Fc gamma RII 阻断可显着消除登革热病毒与 KU812 细胞和 CBMC 的结合。 Fc gamma RII 阻断也抑制登革热病毒感染和 KU812 细胞产生 CCL5。
Dengue virus is a major mosquito-borne human pathogen with four known serotypes. The presence of antidengue virus antibodies in the serum of individuals prior to dengue virus infection is believed to be an important risk factor for severe dengue virus disease as a result of the phenomenon of antibody-dependent enhancement operating on Fe receptor (FcR)-hearing cells. In addition to blood monocytes, mast cells are susceptible to antibody-enhanced dengue virus infection, producing a number of inflammatory mediators including IL-1, IL-6, and CCL5. Using the human mast celllike lines KU812 and HMC-1 as well as primary cultures of human cord blood-derived mast cells (CBMC), we aimed to identify the participating FcRs in antibody-enhanced mast cell dengue virus infection, as FcRs represent a potential site for therapeutic intervention. CBMC expressed significant levels of Fc gamma RI, Fc gamma RII, and Fc gamma RIII, and mast cell-like HMC-1 and KU812 cells expressed predominantly Fc gamma RII. All four serotypes of dengue virus showed antibody-enhanced binding to KU812 cells. Specific Fc gamma RII blockade with mAb IV.3 was found to significantly abrogate dengue virus binding to KU812 cells and CBMC in the presence of dengue-specific antibody. Dengue virus infection and the production of CCL5 by KU812 cells were also inhibited by Fc gamma RII blockade.