Activity of Salmonella SPI-1 inhibits the TLR4-dependent transcriptional but not translational response during macrophage infection
Activity of Salmonella SPI-1 inhibits the TLR4-dependent transcriptional but not translational response during macrophage infection
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DOI：
10.1101/2024.01.08.574706
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发表时间：
2024-01
期刊：
影响因子：
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通讯作者：
George Wood;Rebecca Johnson;Matthew P. Brember;Filip Lastovka;Pani Tourlomousis;Clare Bryant;B. Chung
中科院分区：
文献类型：
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作者：
George Wood;Rebecca Johnson;Matthew P. Brember;Filip Lastovka;Pani Tourlomousis;Clare Bryant;B. Chung
细菌感染过程中基因表达的变化是转录和翻译改变的共同结果，对后者的研究相对较少。革兰氏阴性菌通过激活病原体相关的分子模式受体，例如通过Toll样受体4(TLR4)检测细菌细胞膜上的沙门氏菌脂多糖(LPS)，迅速激活巨噬细胞中的细胞因子基因转录。在这里，通过时间分辨的平行翻译和转录图谱，我们现在显示了TLR4特异性的翻译上调在沙门氏菌诱导的巨噬细胞中的细胞信号蛋白。虽然这些基因的转录上调被沙门氏菌SPI-1三型分泌系统的活性抑制，但仍然存在强大的翻译反应。这些数据揭示了一个重要的宿主-病原体翻译调控网络，它改变了巨噬细胞对感染的先天免疫反应。
Changes in gene expression during bacterial infection are the combined result of altered transcription and translation, with the latter comparatively understudied. Gram-negative bacteria rapidly trigger cytokine gene transcription in macrophages through the activation of pathogen associated molecular pattern receptors, for example detection of Salmonella lipopolysaccharide (LPS) from the bacterial cell envelope by Toll-like receptor 4 (TLR4). Here, through time-resolved parallel translatomic and transcriptomic profiling, we now show temporal TLR4-specific translational upregulation of cell signalling proteins in macrophages induced by Salmonella. While transcriptional upregulation of these genes is dampened through the activity of the Salmonella SPI-1 type three secretion system, a robust translational response remains. These data reveal an important host-pathogen translational regulatory network that modifies the innate immune response of macrophages to infection.