Mycobacterial infection induces a specific human innate immune response.
Mycobacterial infection induces a specific human innate immune response.
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DOI：
10.1038/srep16882
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发表时间：
2015-11-20
影响因子：
4.6
通讯作者：
Gilad Y
中科院分区：
文献类型：
--
作者：
Blischak JD;Tailleux L;Mitrano A;Barreiro LB;Gilad Y
先天免疫系统提供对感染的第一反应，现在被认为是部分病原体特异性的。结核分枝杆菌(MTB)能够颠覆天然免疫反应，在巨噬细胞内存活。奇怪的是，在感染结核杆菌的其他健康个体中，只有5%-10%的人会患上活动性结核病(TB)。我们还不了解这种个体特异性易感性背后的遗传基础。此外，我们仍然不知道哪些先天免疫反应是结核杆菌感染所特有的。为了确定对结核分枝杆菌具有特异性的免疫反应，我们用8种不同的细菌感染巨噬细胞，包括不同的结核分枝杆菌菌株和相关的分枝杆菌，并研究了它们的转录反应。我们确定了一个新的基因子集，其调节受到分枝杆菌感染的特异性影响。这个亚组包括与吞噬小体成熟、超氧化物产生、对维生素D的反应、巨噬细胞趋化和唾液酸合成有关的基因。我们建议，影响这些基因功能或调节的遗传变异应被认为是解释结核病易感性的候选基因。
The innate immune system provides the first response to infection and is now recognized to be partially pathogen-specific. Mycobacterium tuberculosis (MTB) is able to subvert the innate immune response and survive inside macrophages. Curiously, only 5–10% of otherwise healthy individuals infected with MTB develop active tuberculosis (TB). We do not yet understand the genetic basis underlying this individual-specific susceptibility. Moreover, we still do not know which properties of the innate immune response are specific to MTB infection. To identify immune responses that are specific to MTB, we infected macrophages with eight different bacteria, including different MTB strains and related mycobacteria, and studied their transcriptional response. We identified a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. This subset includes genes involved in phagosome maturation, superoxide production, response to vitamin D, macrophage chemotaxis, and sialic acid synthesis. We suggest that genetic variants that affect the function or regulation of these genes should be considered candidate loci for explaining TB susceptibility.