Oral recombinant human or mouse lactoferrin reduces Mycobacterium tuberculosis TDM induced granulomatous lung pathology
Oral recombinant human or mouse lactoferrin reduces Mycobacterium tuberculosis TDM induced granulomatous lung pathology
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DOI：
10.1139/bcb-2016-0061
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发表时间：
2017-02-01
影响因子：
2.9
通讯作者：
Actor, Jeffrey K.
中科院分区：
文献类型：
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作者：
Hwang, Shen-An;Kruzel, Marian L.;Actor, Jeffrey K.
海藻糖(TDM)是结核分枝杆菌(MTB)细胞壁上含量最丰富的糖脂。TDM能够在小鼠模型中诱发肉芽肿性病理，类似于MTB感染所致的病理。利用急性TDM模型，研究重组人和小鼠乳铁蛋白对减少肉芽肿性病变的作用。给C57BL/6小鼠静脉注射TDM，剂量为25MU·g·g-1。第4天和第6天，灌胃给予重组人或小鼠乳铁蛋白(1 mg.(百亩L)(-1).小鼠(-1))。在注射TDM后的第7天，对小鼠的肺病理、细胞因子产生和白细胞数量进行评估。给予人或小鼠乳铁蛋白的小鼠肺中IL-12p40的产生减少。小鼠乳铁蛋白增加肺组织中IL-6和KC(CXCL1)的表达。在注射TDM的小鼠中，观察到给予人或小鼠乳铁蛋白的巨噬细胞数量增加。肉芽肿性病变，主要由迁移的白细胞组成，在接受人类或小鼠乳铁蛋白治疗的小鼠中，肉芽肿性病理明显减轻。肉芽肿性病理的定量检测显示，与TDM对照组相比，服用人或小鼠乳铁蛋白的小鼠显著减少。本报告首次直接比较了异源重组人乳铁蛋白和同源小鼠乳铁蛋白在TDM诱导的肉芽肿形成过程中的免疫调节作用。
Trehalose 6'6-dimycolate (TDM) is the most abundant glycolipid on the cell wall of Mycobacterium tuberculosis (MTB). TDM is capable of inducing granulomatous pathology in mouse models that resembles those induced by MTB infection. Using the acute TDM model, this work investigates the effect of recombinant human and mouse lactoferrin to reduce granulomatous pathology. C57BL/6 mice were injected intravenously with TDM at a dose of 25 mu g. mouse(-1). At day 4 and 6, recombinant human or mouse lactoferrin (1 mg.(100 mu L)(-1).mouse(-1)) were delivered by gavage. At day 7 after TDM injection, mice were evaluated for lung pathology, cytokine production, and leukocyte populations. Mice given human or mouse lactoferrin had reduced production of IL-12p40 in their lungs. Mouse lactoferrin increased IL-6 and KC (CXCL1) in lung tissue. Increased numbers of macrophages were observed in TDM-injected mice given human or mouse lactoferrin. Granulomatous pathology, composed of mainly migrated leukocytes, was visually reduced in mice that received human or mouse lactoferrin. Quantitation of granulomatous pathology demonstrated a significant decrease in mice given human or mouse lactoferrin compared with TDM control mice. This report is the first to directly compare the immune modulatory effects of both heterologous recombinant human and homologous mouse lactoferrin on the development of TDM-induced granulomas.