Giebeler Liane, Ehrhardt Christina, Häder Antje, Lauf Thurid, Deinhardt-Emmer Stefanie, Löffler Bettina
Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, 07745 Jena, Germany.
Institute of Medical Microbiology, Jena University Hospital, 07747 Jena, Germany.
Int J Mol Sci. 2025 Jun 3;26(11):5364. doi: 10.3390/ijms26115364.
A diverse bacterial community colonizes the respiratory system, including commensals such as and , as well as facultative pathogens like . This study aimed to establish a colonized cell culture model to investigate the impact of these bacteria on influenza A virus (IAV) infection. Respiratory epithelial cells were exposed to , , or , using either live or heat-inactivated bacteria, followed by IAV infection. Cell integrity was assessed microscopically, cytotoxicity was measured via LDH assay, and inflammatory responses were analyzed through cytokine expression. Additionally, macrophage function was examined in response to bacterial colonization and IAV infection. While commensals maintained epithelial integrity for 48 h, induced severe cell damage and death. The most pronounced epithelial destruction was caused by coinfection with and IAV. Notably, commensals did not confer protection against IAV but instead enhanced epithelial inflammation. These effects were dependent on live bacteria, as inactivated bacteria had no impact. However, prior exposure to and improved macrophage-mediated immune responses against IAV. These findings suggest that while individual commensals do not directly protect epithelial cells, they may contribute to immune training and enhance lung defense mechanisms.
多种细菌群落定殖于呼吸系统，包括共生菌如[具体共生菌1]和[具体共生菌2]，以及兼性病原菌如[具体兼性病原菌]。本研究旨在建立一种定殖细胞培养模型，以研究这些细菌对甲型流感病毒（IAV）感染的影响。将呼吸道上皮细胞暴露于[具体细菌1]、[具体细菌2]或[具体细菌3]，使用活细菌或热灭活细菌，随后进行IAV感染。通过显微镜评估细胞完整性，通过乳酸脱氢酶（LDH）测定法测量细胞毒性，并通过细胞因子表达分析炎症反应。此外，还检测了巨噬细胞对细菌定殖和IAV感染的反应功能。虽然共生菌在48小时内维持上皮完整性，但[具体细菌]导致严重的细胞损伤和死亡。最明显的上皮破坏是由[具体细菌]与IAV共感染引起的。值得注意的是，共生菌并未赋予对IAV的保护作用，反而增强了上皮炎症。这些效应依赖于活细菌，因为灭活细菌没有影响。然而，先前暴露于[具体细菌1]和[具体细菌2]可改善巨噬细胞介导的针对IAV的免疫反应。这些发现表明，虽然单个共生菌不会直接保护上皮细胞，但它们可能有助于免疫训练并增强肺部防御机制。
