High mortality of Acinetobacter baumannii infection is attributed to macrophage_mediated induction of cytokine storm

Acinetobacter baumannii is one of the bacterial pathogens that commonly causes hospital-acquired infections, for which the mortality rate was estimated to be as high as 26.0% to 55.7% in different countries. The continuous emergence of multidrug-resistant (MDR) strains of this pathogen poses further challenges to clinical management of A. baumannii infections. It is necessary to explore unconventional strategies to control outbreaks of drug-resistant infections. In this work, we conducted a study of the host immune response elicited by A. baumannii. The results highlighted the critical role of alveolar and interstitial macrophages as targets of Ab during the infection process, as these cells were found to undergo polarization towards the M1 phenotype, triggering a cytokine storm that eventually caused the death of the host. The polarization and excessive inflammatory response mediated by macrophages were mainly regulated by the TLR2/Myd88/NfkB signaling pathway. Findings in this work depicted the major mechanisms underlying the high mortality rate of A. baumannii infections.鲍曼不动杆菌（Acinetobacter baumannii）是引发医院获得性感染的常见致病菌之一，据估算不同国家中该类感染的死亡率可达26.0%至55.7%。该致病菌的多重耐药（multidrug-resistant, MDR）菌株持续出现，进一步为鲍曼不动杆菌感染的临床管理带来挑战。探索非常规策略以控制耐药感染暴发已颇具必要性。本研究针对鲍曼不动杆菌诱导的宿主免疫应答展开分析。研究结果揭示，肺泡与间质巨噬细胞作为鲍曼不动杆菌感染过程中的靶标发挥着关键作用：研究发现此类细胞极化为M1表型，进而触发细胞因子风暴，最终导致宿主死亡。巨噬细胞介导的极化与过度炎症反应主要受TLR2/Myd88/NfkB信号通路调控。本研究的发现阐明了鲍曼不动杆菌感染高死亡率的核心机制。