Primary macrophages and J774 cells respond differently to infection with Mycobacterium tuberculosis.
Primary macrophages and J774 cells respond differently to infection with Mycobacterium tuberculosis.
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DOI：
10.1038/srep42225
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发表时间：
2017-02-08
影响因子：
4.6
通讯作者：
Hibberd ML
中科院分区：
文献类型：
--
作者：
Andreu N;Phelan J;de Sessions PF;Cliff JM;Clark TG;Hibberd ML
巨噬细胞在早期对结核分枝杆菌的免疫应答中起重要作用，是体内优先感染的细胞类型。原代巨噬细胞和巨噬细胞样细胞系通常被用作感染模型，尽管细胞系的生理相关性，特别是在宿主-病原体相互作用研究中，是有争议的。在这里，我们使用高通量rna测序来分析两种巨噬细胞模型对结核分枝杆菌感染的转录组动力学反应。具体来说，我们研究了骨髓来源的小鼠巨噬细胞和细胞系J774对活的和γ辐照（杀死）结核分枝杆菌感染的早期反应。我们发现，活杆菌感染特异性地改变了宿主基因如Rsad2、Ifit1/2/3和rig - 1的表达，这些基因在抵抗结核分枝杆菌感染中的潜在作用尚未被研究。此外，从差异表达基因的数量和诱导/抑制的程度来看，原代巨噬细胞的反应比J774细胞更快、更强烈。我们的研究结果指出了在结核分枝杆菌感染早期导致免疫遏制的潜在新过程，并支持了原代巨噬细胞和细胞系之间存在重要差异的观点，在选择巨噬细胞模型来研究宿主-病原体相互作用时应考虑到这一点。
Macrophages play an essential role in the early immune response to Mycobacterium tuberculosis and are the cell type preferentially infected in vivo. Primary macrophages and macrophage-like cell lines are commonly used as infection models, although the physiological relevance of cell lines, particularly for host-pathogen interaction studies, is debatable. Here we use high-throughput RNA-sequencing to analyse transcriptome dynamics of two macrophage models in response to M. tuberculosis infection. Specifically, we study the early response of bone marrow-derived mouse macrophages and cell line J774 to infection with live and γ-irradiated (killed) M. tuberculosis. We show that infection with live bacilli specifically alters the expression of host genes such as Rsad2, Ifit1/2/3 and Rig-I, whose potential roles in resistance to M. tuberculosis infection have not yet been investigated. In addition, the response of primary macrophages is faster and more intense than that of J774 cells in terms of number of differentially expressed genes and magnitude of induction/repression. Our results point to potentially novel processes leading to immune containment early during M. tuberculosis infection, and support the idea that important differences exist between primary macrophages and cell lines, which should be taken into account when choosing a macrophage model to study host-pathogen interactions.