To understand toxin-stimulated host-pathogen interactions, we performed dual-transcriptome sequencing experiments using human epithelial (HT-29) and differentiated THP-1 (dTHP-1) immune cells infected with the sepsis-causing pathogen Vibrio vulnificus (either the wild-type [WT] pathogen or a multifunctional-autoprocessing repeats-in-toxin [MARTX] toxin-deficient strain). Gene set enrichment analyses revealed MARTX toxin-dependent responses, including negative regulation of extracellular related kinase 1 (ERK1) and ERK2 (ERK1/2) signaling and cell cycle regulation in HT-29 and dTHP-1 cells, respectively. Further analysis of the expression of immune-related genes suggested that the MARTX toxin dampens immune responses in gut epithelial cells but accelerates inflammation and nuclear factor κB (NF-κB) signaling in immune cells. With respect to the pathogen, siderophore biosynthesis genes were significantly more highly expressed in WT V. vulnificus than in the MARTX toxin-deficient mutant upon infection of dTHP-1 cells. Consistent with these results, iron homeostasis genes that limit iron levels for invading pathogens were overexpressed in WT V. vulnificus-infected dTHP-1 cells. Taken together, these results suggest that MARTX toxin regulates host inflammatory responses during V. vulnificus infection while also countering host defense mechanisms such as iron limitation.

中文翻译：

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MARTX 毒素刺激的人类细胞和创伤弧菌之间的相互作用。

为了了解毒素刺激的宿主-病原体相互作用，我们使用感染了败血症病原体创伤弧菌（野生弧菌）的人上皮 (HT-29) 和分化的 THP-1 (dTHP-1) 免疫细胞进行了双转录组测序实验。型[WT]病原体或米ultifunctional-一个utoprocessing ř epeats-IN-吨ø X在 [MARTX] 毒素缺陷菌株中）。基因集富集分析揭示了 MARTX 毒素依赖性反应，包括细胞外相关激酶 1 (ERK1) 和 ERK2 (ERK1/2) 信号传导的负调节以及 HT-29 和 dTHP-1 细胞中的细胞周期调节。对免疫相关基因表达的进一步分析表明，MARTX 毒素会抑制肠道上皮细胞的免疫反应，但会加速免疫细胞中的炎症和核因子 κB (NF-κB) 信号传导。对于病原体，在感染 dTHP-1 细胞后，铁载体生物合成基因在 WT V. vulnificus中的表达比在 MARTX 毒素缺陷突变体中高得多。与这些结果一致，限制入侵病原体铁水平的铁稳态基因在 WT 中过表达创伤弧菌感染的 dTHP-1 细胞。总之，这些结果表明 MARTX 毒素在创伤弧菌感染期间调节宿主炎症反应，同时还对抗宿主防御机制，如铁限制。