Siderocalin inhibits the intracellular replication of Mycobacterium tuberculosis in macrophages.
Siderocalin inhibits the intracellular replication of Mycobacterium tuberculosis in macrophages.
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DOI：
10.1111/j.1574-695x.2009.00622.x
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发表时间：
2010-02
影响因子：
--
通讯作者：
Cherayil BJ
中科院分区：
文献类型：
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作者：
Johnson EE;Srikanth CV;Sandgren A;Harrington L;Trebicka E;Wang L;Borregaard N;Murray M;Cherayil BJ
铁载体蛋白是一种分泌性蛋白质，它与铁载体结合以阻止细菌获得铁。虽然它已被证明可以抑制结核分枝杆菌（M.tb）在细胞外培养物中的生长，但其对巨噬细胞内这种病原体的影响尚不清楚。在这里，我们表明，铁载体蛋白表达上调结核分枝杆菌感染小鼠巨噬细胞系和原代小鼠肺泡巨噬细胞。此外，外源添加的重组蛋白或在RAW264.7巨噬细胞系中过表达的铁黄素抑制病原体的细胞内生长。一种仅在巨噬细胞胞质溶胶中表达的含铁菌素的变体形式，与正常分泌形式一样有效地抑制细胞内结核分枝杆菌生长，这一观察结果提供了对含铁菌素如何影响吞噬体中细菌的铁获取的机理性见解。我们的研究结果是一致的重要作用，铁在保护结核分枝杆菌感染，并建议外源性管理的铁可能有治疗结核病的应用。
Siderocalin is a secreted protein that binds to siderophores to prevent bacterial iron acquisition. While it has been shown to inhibit the growth of Mycobacterium tuberculosis (M.tb) in extracellular cultures, its effect on this pathogen within macrophages is not clear. Here, we show that siderocalin expression is up-regulated following M.tb infection of mouse macrophage cell lines and primary murine alveolar macrophages. Furthermore, siderocalin added exogenously as a recombinant protein or over-expressed in the RAW264.7 macrophage cell line inhibited the intracellular growth of the pathogen. A variant form of siderocalin, which is expressed only in the macrophage cytosol, inhibited intracellular M.tb growth as effectively as the normal, secreted form, an observation that provides mechanistic insight into how siderocalin might influence iron acquisition by the bacteria in the phagosome. Our findings are consistent with an important role for siderocalin in protection against M.tb infection and suggest that exogenously administered siderocalin may have therapeutic applications in tuberculosis.