Hu Renjing, Wan Lin, Liu Xiaoyun, Lu Jie, Hu Xichi, Zhang Xiaoli, Zhang Min
Department of Laboratory Medicine, Jiangnan University Medical Center, Wuxi, China.
Center Laboratory, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
J Thorac Dis. 2023 Aug 31;15(8):4396-4412. doi: 10.21037/jtd-23-493. Epub 2023 Aug 15.
As the first line of defense, epithelial cells play a vital role in the initiation and control of both innate and adaptive immunity, which participate in the development of disease. Despite its therapeutic significance, little is understood about the specific interaction between pathogenic microorganisms and lung epithelial cells.
In this study, we performed a head-to-head comparison of the virulence and infection mechanisms of () and (), which represent Gram-negative/positive respiratory pathogens, respectively, in lung epithelial cell models for the first time.
Through scanning electron microscopy combined with bacterial infection experiments, we confirmed the ability of and strains to form biofilm and cord factor out of the cell wall. has stronger adhesion and intracellular retention ability, while is more likely to induce acute infection. These pathogens could stay and proliferate in lung epithelial cells and stimulate the secretion of specific cytokines and chemokines through a gene transcription regulator. infection can promote crosstalk among epithelial cells and other immune cells in the lung from a very early stage by prompting the secretion of pro-inflammatory cytokines. Meanwhile, there were significant correlations between infection and higher levels of interleukin-15 (IL-15), interleukin-1Rα (IL-1Rα), fibroblast growth factor (FGF) basic, and granulocyte colony-stimulating factor (G-CSF). At the same time, infection also led to changes in the expression of cytoskeletal proteins in epithelial cells.
Our results emphasized the immunoprotection and immunomodulation of lung epithelial cells against exogenous pathogenic microorganisms, indicating that different pathogens damaged the host through different strategies and induced varying innate immune responses. At the same time, they provided important clues and key immune factors for dealing with complicated pulmonary infections.
作为第一道防线，上皮细胞在先天性和适应性免疫的启动与控制中发挥着至关重要的作用，而这两种免疫都参与疾病的发展。尽管其具有治疗意义，但对于致病微生物与肺上皮细胞之间的具体相互作用却知之甚少。
在本研究中，我们首次在肺上皮细胞模型中对分别代表革兰氏阴性/阳性呼吸道病原体的（）和（）的毒力及感染机制进行了直接比较。
通过扫描电子显微镜结合细菌感染实验，我们证实了和菌株在细胞壁外形成生物膜和索状因子的能力。具有更强的黏附及细胞内留存能力，而更易引发急性感染。这些病原体可在肺上皮细胞中停留并增殖，并通过一种基因转录调节因子刺激特定细胞因子和趋化因子的分泌。感染可通过促使促炎细胞因子的分泌，从早期就促进肺上皮细胞与其他免疫细胞之间的串扰。同时，感染与白细胞介素 -15（IL -15）、白细胞介素 -1Rα（IL -1Rα）、碱性成纤维细胞生长因子（FGF）和粒细胞集落刺激因子（G -CSF）水平升高之间存在显著相关性。同时，感染还导致上皮细胞中细胞骨架蛋白表达的变化。
我们的结果强调了肺上皮细胞对外源致病微生物的免疫保护和免疫调节作用，表明不同病原体通过不同策略损害宿主并诱导不同的先天性免疫反应。同时，它们为应对复杂的肺部感染提供了重要线索和关键免疫因子。
