Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea.
College of Veterinary Medicine, Kyungpook National University, Daegu, South Korea.
Front Cell Infect Microbiol. 2017 Oct 9;7:437. doi: 10.3389/fcimb.2017.00437. eCollection 2017.
In this study, we explore the regulatory roles of pro-inflammatory cytokine tumor necrosis factor alpha (TNF) in the innate immunity of macrophages against infection. We show that infection of macrophage with induces marked expression and secretion of TNF which subsequently binds to TNF receptor 1 (TNFR-1) and activates a downstream signaling cascade of the innate immunity. Blocking of TNF signaling resulted in a notable increase of survival which was associated with an increase of anti-inflammatory cytokine interleukin 10 (IL-10), a beneficial effector of survival, as well as remarkable decrease of reactive oxygen species (ROS) and nitric oxide (NO), antibrucella molecules. However, surprisingly, the interference of TNF did not show any influence on phagolysosome and cell death events. Furthermore, the transcriptional factor NF-B was found to be a main mediator of TNF signaling when blocking of NF-B pathway drastically suppressed the TNF-induced brucellacidal effect. Taken together, these findings clearly indicate that the immune cascade activated by TNF/TNFR-1 is required for the sufficient resistance to survival in macrophages.
在这项研究中，我们探讨了促炎细胞因子肿瘤坏死因子-α（TNF）在巨噬细胞固有免疫抵抗感染中的调节作用。我们发现，感染巨噬细胞会导致 TNF 的显著表达和分泌，随后 TNF 与 TNF 受体 1（TNFR-1）结合并激活固有免疫的下游信号级联反应。阻断 TNF 信号会导致显著增加的存活，这与抗炎细胞因子白细胞介素 10（IL-10）的增加有关，IL-10 是 存活的有益效应物，同时还会导致活性氧（ROS）和一氧化氮（NO）的显著减少，这是抗布鲁氏菌的分子。然而，令人惊讶的是，干扰 TNF 并没有显示出对吞噬体和细胞死亡事件的任何影响。此外，发现转录因子 NF-B 是 TNF 信号通路的主要介导者，因为阻断 NF-B 途径会大大抑制 TNF 诱导的布鲁氏菌杀菌作用。综上所述，这些发现清楚地表明，TNF/TNFR-1 激活的免疫级联反应对于巨噬细胞中对布鲁氏菌的充分抵抗是必需的。
