The inappropriate use of antibiotics is a severe public health problem worldwide, contributing to the emergence of multidrug-resistant (MDR) bacteria. To explore the possible impacts of the inappropriate use of antibiotics on the immune system, we use Klebsiella pneumoniae (K. pneumoniae) infection as an example and show that imipenem increases the mortality of mice infected by MDR K. pneumoniae. Further studies demonstrate that imipenem enhances the secretion of outer membrane vesicles (OMVs) with significantly elevated presentation of GroEL, which promotes the phagocytosis of OMVs by macrophages that depends on the interaction between GroEL and its receptor, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). OMVs cause the pyroptosis of macrophages and the release of proinflammatory cytokines, which contribute to exacerbated inflammatory responses. We propose that the inappropriate use of antibiotics in the cases of infection by MDR bacteria such as K. pneumoniae might cause damaging inflammatory responses, which underlines the pernicious effects of inappropriate use of antibiotics.

抗生素的不当使用是世界范围内一个严重的公共卫生问题，导致多重耐药 (MDR) 细菌的出现。为了探讨抗生素使用不当对免疫系统可能产生的影响，我们以肺炎克雷伯菌（K.pneumoniae）感染为例，表明亚胺培南会增加感染 MDR K.pneumoniae的小鼠的死亡率. 进一步的研究表明，亚胺培南可增强外膜囊泡 (OMV) 的分泌，并显着提高 GroEL 的呈递，从而促进巨噬细胞对 OMV 的吞噬作用，这取决于 GroEL 与其受体凝集素样氧化低密度脂蛋白受体之间的相互作用-1 (LOX-1)。OMV 引起巨噬细胞的焦亡和促炎细胞因子的释放，从而加剧炎症反应。我们认为，在肺炎克雷伯菌等耐多药细菌感染的情况下，不当使用抗生素可能会导致破坏性炎症反应，这突显了不当使用抗生素的有害影响。