Department of Pharmacy and Pharmacology, University of Bath, BA2 7AY, UK.
J Med Microbiol. 2019 Dec;68(12):1813-1822. doi: 10.1099/jmm.0.001100.
Chronic pulmonary infection is associated with colonization with multiple micro-organisms but host-microbe and microbe-microbe interactions are poorly understood. This study aims to investigate the differences in host responses to mono- and co-infection with and in human airway epithelial cells. We assessed the effect of co-infection with and on host signalling and inflammatory responses in the human airway epithelial cell line 16HBE, using ELISA and western blot analysis. The results show that activates MAPK and NF-κB signalling pathways, subsequently eliciting robust interleukin (IL)-8 production. However, when airway epithelial cells were co-treated with live bacteria and supernatants (conditioned medium), the pro-inflammatory response was attenuated. This anti-inflammatory effect was widely exhibited in the isolates tested and was mediated via reduced MAPK and NF-κB signalling, but not via IL-1 receptor or tumour necrosis factor receptor modulation. The staphylococcal effectors were characterized as small, heat-stable, non-proteinaceous and not cell wall-related factors. This study demonstrates for the first time the host response in a / co-infection model and provides insight into a staphylococcal immune evasion mechanism, as well as a therapeutic intervention for excessive inflammation.
慢性肺部感染与多种微生物的定植有关，但宿主-微生物和微生物-微生物之间的相互作用尚不清楚。本研究旨在研究人类气道上皮细胞中单重和双重感染与 和 时宿主反应的差异。我们使用 ELISA 和 Western blot 分析评估了 和 共感染对人气道上皮细胞系 16HBE 中宿主信号转导和炎症反应的影响。结果表明， 激活 MAPK 和 NF-κB 信号通路，随后引发强烈的白细胞介素 (IL)-8 产生。然而，当气道上皮细胞同时用活 细菌和 上清液（条件培养基）处理时，促炎反应减弱。这种抗炎作用在测试的 分离株中广泛表现，并通过减少 MAPK 和 NF-κB 信号转导介导，而不是通过 IL-1 受体或肿瘤坏死因子受体调节。葡萄球菌效应物的特征是小、耐热、非蛋白和与细胞壁无关的因子。本研究首次在 / 共感染模型中展示了宿主反应，并为葡萄球菌免疫逃避机制以及过度炎症的治疗干预提供了新的见解。
