创伤弧菌 (Vv) 已知会引起危及生命的感染，特别是败血症。这些患者通常表现出促炎细胞因子水平升高。虽然已确定丝裂原激活蛋白激酶 (MAPK) 相互作用激酶 (MNK) 有助于促炎细胞因子的产生，但 MNK 在 Vv 感染期间巨噬细胞中的作用仍不清楚。在这项研究中，我们研究了 MNK 对巨噬细胞的影响。我们证明，当用脂多糖或 Vv 处理时，J774A.1 细胞中 MNK 的抑制导致肿瘤坏死因子 α 和白细胞介素 6 的产生减少，而不影响其转录。有趣的是，用 MNK 抑制剂 CGP57380 治疗导致 MNK1 磷酸化增强，但 eIF4E 磷酸化降低。此外，MNK1 敲除细胞表现出吞噬作用和 Vv 清除能力增强，具有比亲代细胞更多的酸性吞噬体。值得注意的是，CGP57380 不会影响 Vv 感染的 J774A.1 细胞中的吞噬作用、细菌清除或吞噬体酸化。考虑到已报道的 MNK 与哺乳动物雷帕霉素复合物 1 (mTORC1) 激活靶点之间的关联，我们研究了感染 Vv 的 MNK1 敲除细胞中的 mTORC1 信号传导。我们的结果表明，这些细胞中 mTORC1 信号传导的减弱以及 mTORC1 抑制剂雷帕霉素的治疗显着增强了 Vv 感染后 J774A.1 细胞中的细菌清除率。总之，我们的研究结果表明，MNK 促进 J774A.1 细胞中 Vv 诱导的细胞因子产生，而不影响其转录水平。 MNK1 似乎通过 MNK1-mTORC1 信号通路而不是 MNK1-eIF4E 信号通路损害 Vv 感染的 J774A.1 细胞中的吞噬作用、细菌清除和吞噬体酸化。我们的研究结果强调了 MNK1-mTORC1 通路在调节巨噬细胞对 Vv 感染的反应中的重要性。丝裂原激活蛋白激酶 (MAPK) 相互作用激酶 (MNK) 在促进肿瘤坏死因子 α 和白细胞介素 6 的产生中发挥作用。创伤弧菌（Vv）感染期间的巨噬细胞。 J774A.1 细胞中 MNK1 的抑制或敲除会导致细胞因子产生减少，但不影响其转录水平。 MNK1 还通过 MNK1-哺乳动物雷帕霉素靶蛋白复合物 1 (mTORC1) 信号通路损害 Vv 感染细胞中的吞噬作用、细菌清除和吞噬体酸化。这些发现强调了 MNK1-mTORC1 通路在调节巨噬细胞对 Vv 感染反应中的重要性。

Vibrio vulnificus (Vv) is known to cause life-threatening infections, particularly septicemia. These patients often exhibit elevated levels of pro-inflammatory cytokines. While it is established that mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) contributes to the production of pro-inflammatory cytokines, the role of MNK in macrophages during Vv infection remains unclear. In this study, we investigate the impact of MNK on macrophages. We demonstrate that the inhibition of MNK in J774A.1 cells, when treated with lipopolysaccharide or Vv, resulted in decreased production of tumor necrosis factor alpha and interleukin-6, without affecting their transcription. Interestingly, treatment with MNK inhibitor CGP57380 led to enhanced phosphorylation of MNK1 but decreased phosphorylation of eIF4E. Moreover, MNK1 knockout cells exhibited an increased capacity for phagocytosis and clearance of Vv, with more acidic phagosomes than the parental cells. Notably, CGP57380 did not impact phagocytosis, bacterial clearance, or phagosome acidification in Vv-infected J774A.1 cells. Considering the reported association between MNK and mammalian target of rapamycin complex 1 (mTORC1) activation, we investigated the mTORC1 signaling in MNK1 knockout cells infected with Vv. Our results revealed that attenuation of the mTORC1 signaling in these cells and treatment with the mTORC1 inhibitor rapamycin significantly enhanced bacterial clearance in J774A.1 cells following Vv infection. In summary, our findings suggest that MNK promotes the Vv-induced cytokine production in J774A.1 cells without affecting their transcription levels. MNK1 appears to impair the phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected J774A.1 cells through the MNK1-mTORC1 signaling pathway rather than the MNK1-eIF4E signaling pathway. Our findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection.Mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) plays a role in promoting the production of tumor necrosis factor alpha and interleukin-6 in macrophages during Vibrio vulnificus (Vv) infection. Inhibition or knockout of MNK1 in J774A.1 cells resulted in reduced cytokine production without affecting their transcription levels. MNK1 also impairs phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected cells through the MNK1-mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. The findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection.