Hwang Shen-An, Kruzel Marian L, Actor Jeffrey K
Department of Pathology, University of Texas-Houston Medical School, Houston, TX, USA.
Department of Integrative Biology and Pharmacology, University of Texas-Houston Medical School, Houston, TX, USA.
Innate Immun. 2015 Jul;21(5):553-61. doi: 10.1177/1753425914564609. Epub 2014 Dec 23.
Lactoferrin (LF), a natural iron-binding protein, has previously demonstrated effectiveness in enhancing the Bacillus Calmette-Guérin (BCG) tuberculosis vaccine. This report investigates immune modulatory effects of Chinese hamster ovary (CHO) cell-expressed recombinant mouse and human LFs on mouse bone marrow-derived dendritic cells (BMDCs), comparing homologous and heterologous functions. BCG-infected BMDCs were cultured with LF, and examined for class II presentation molecule expression. Culturing of BCG-infected BMDCs with either LF decreased the class II molecule-expressing population. Mouse LF significantly increased the production of IL-12p40, IL-1β and IL-10, while human LF-treated BMDCs increased only IL-1β and IL-10. Overlaying naïve CD4 T-cells onto BCG-infected BMDCs cultured with mouse LF increased IFN-γ, whereas the human LF-exposed group increased IFN-γ and IL-17 from CD4 T cells. Overlay of naïve CD8 T cells onto BCG-infected BMDCs treated with mouse LF increased the production of IFN-γ and IL-17, while similar experiments using human LF only increased IL-17. This report is the first to examine mouse and human recombinant LFs in parallel experiments to assess murine DC function. These results detail the efficacy of the human LF counterpart used in a heterologous system to understand LF-mediated events that confer BCG efficacy against Mycobacterium tuberculosis challenge.
乳铁蛋白（LF）是一种天然的铁结合蛋白，此前已证明其在增强卡介苗（BCG）结核病疫苗方面具有有效性。本报告研究了中国仓鼠卵巢（CHO）细胞表达的重组小鼠和人乳铁蛋白对小鼠骨髓来源的树突状细胞（BMDC）的免疫调节作用，比较了同源和异源功能。将感染卡介苗的BMDC与乳铁蛋白一起培养，并检测II类呈递分子的表达。用乳铁蛋白培养感染卡介苗的BMDC会减少表达II类分子的细胞群体。小鼠乳铁蛋白显著增加了IL-12p40、IL-1β和IL-10的产生，而用人乳铁蛋白处理的BMDC仅增加了IL-1β和IL-10。将未活化的CD4 T细胞覆盖在与小鼠乳铁蛋白一起培养的感染卡介苗的BMDC上会增加IFN-γ的产生，而用人乳铁蛋白处理的组会使CD4 T细胞增加IFN-γ和IL-17。将未活化的CD8 T细胞覆盖在用小鼠乳铁蛋白处理的感染卡介苗的BMDC上会增加IFN-γ和IL-17的产生，而使用人乳铁蛋白的类似实验仅增加了IL-17。本报告首次在平行实验中检测小鼠和人重组乳铁蛋白以评估小鼠树突状细胞功能。这些结果详细说明了在异源系统中使用的人乳铁蛋白对应物的功效，以了解赋予卡介苗抗结核分枝杆菌攻击效力的乳铁蛋白介导的事件。
