Phagocytosis of a Model Human Immunodeficiency Virus Target by Human Breast Milk Leukocytes Is Predominantly Granulocyte-Driven When Elicited by Specific Antibody.
Phagocytosis of a Model Human Immunodeficiency Virus Target by Human Breast Milk Leukocytes Is Predominantly Granulocyte-Driven When Elicited by Specific Antibody.
复制标题
当特定抗体引发时，人母乳白细胞对人类免疫缺陷病毒模型靶标的吞噬作用主要是粒细胞驱动的。
DOI：
10.1089/bfm.2018.0232
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Itri,Vincenza
中科院分区：
文献类型：
--
作者：
Powell,RebeccaLR;Fox,Alisa;Liu,Xiaomei;Itri,Vincenza
背景：研究表明母乳中的抗体（Abs）对人类免疫缺陷病毒（HIV）母婴传播（MTCT）具有保护作用。BM细胞成分的贡献一直被忽视。唯一证明有效的临床HIV疫苗试验RV144通过恒定免疫球蛋白区结晶片段（Fc）将保护作用与抗体介导的功能联系起来。这些数据支持白细胞通过Fc受体（FcRs）诱导疫苗抗体触发抗病毒活性。目的：检测抗体依赖性细胞吞噬作用（ADCP），这是一种重要的fc介导的吞噬细胞反应。材料和方法：从5个产后7-183天的人乳腺样本中分离细胞，分析ADCP。以HIV包膜（Env）表位包被的荧光珠为靶标。使用了67至100毫升的牛奶。结果：每毫升总细胞浓度为16,083-222,857，CD45+白细胞占1.6-12.3%。ADCP活性用hiv特异性Ab 830A测定。使用肌动蛋白抑制剂细胞松弛素D和FcR阻滞剂表明ADCP是肌动蛋白依赖的，需要FcR参与。在所研究的样本中，ADCP评分是可变的，但在很大程度上是一致的，从CD45+细胞的最低活性到最高活性的差异小于4倍。在CD45+ADCP中，粒细胞衍生的活性明显更多（72-95%），而其余活性由单核细胞驱动。结论：这些数据表明，骨髓吞噬细胞在特异性抗体存在的情况下可以表现出抗病毒活性，因此可能有助于降低HIV的MTCT。
Background:Studies demonstrate a protective effect of antibodies (Abs) in breast milk (BM) against mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Contribution of the BM cellular component has been overlooked. The only clinical HIV vaccine trial to demonstrate efficacy, RV144, correlated protection with Abs mediating functions through the constant immunoglobulin region—the crystallizable fragment (Fc). These data support induction of vaccine Abs triggering antiviral activities by leukocytes through Fc receptors (FcRs).Objective:To measure Ab-dependent cellular phagocytosis (ADCP), an essential Fc-mediated response, by BM phagocytes.Materials and Methods:Cells were isolated from five human BM samples obtained at 7–183 days postpartum and analyzed for ADCP. Fluorescent beads coated with HIV envelope (Env) epitopes were used as targets. Sixty-seven to 100 mL of milk was utilized.Results:Total cell concentrations per milliliter were 16,083–222,857, with 1.6–12.3% being CD45+leukocytes. ADCP activity was measurable using the HIV-specific Ab 830A. Use of the actin inhibitor cytochalasin D and FcR blocker indicated that ADCP was actin dependent and required FcR engagement. ADCP scores were variable, but largely consistent, across the samples studied, exhibiting <4-fold difference from lowest to highest activity for CD45+cells. Of the CD45+ADCP, significantly more activity was granulocyte derived (72–95%), while the remaining activity was monocyte driven.Conclusions:The data indicate that BM phagocytes can manifest antiviral activities in the presence of specific Abs and therefore may contribute to reduction of MTCT of HIV.