International Journal of Medical Microbiology ( IF 4.1 ) Pub Date : 2023-01-20 , DOI: 10.1016/j.ijmm.2023.151574 Lei Yue 1 , Han Cao 1 , Jialong Qi 2 , Jin Yuan 3 , Xin Wang 3 , Yunfei Wang 1 , Bin Shan 4 , Huaxin Ke 1 , Hua Li 1 , Ning Luan 1 , Cunbao Liu 1
Pseudomonas aeruginosa is one of the leading causes of nosocomial infections worldwide. Clinical isolates that are resistant to multiple antimicrobials make it intractable. The interactions between P. aeruginosa and host cell death have multiple effects on bacterial clearance and inflammation; however, the potential intervention effects remain to be defined. Herein, we demonstrated that intravenous administration of 3-methyladenine before, but not after, P. aeruginosa infection enhanced autophagy-independent survival, which was accompanied by a decrease in the bacterial load, alleviation of pathology and reduction in inflammatory cytokines, in an acute pneumonia mouse model. Interestingly, these beneficial effects were not dependent on neutrophil recruitment or phagocytosis, but on the enhanced killing capacity induced by inhibiting the cell death of 3-MA pretreated neutrophils. These findings demonstrate a novel protective role of 3-MA pretreatment in P. aeruginosa-induced acute pneumonia.
中文翻译:
小鼠感染模型中,3-甲基腺嘌呤预处理通过抑制中性粒细胞死亡改善铜绿假单胞菌引起的急性肺炎
铜绿假单胞菌是全世界医院感染的主要原因之一。对多种抗菌药物具有耐药性的临床分离株使其难以处理。铜绿假单胞菌与宿主细胞死亡之间的相互作用对细菌清除和炎症具有多重影响;然而,潜在的干预效果仍有待确定。在此,我们证明了在铜绿假单胞菌之前而不是之后静脉注射 3-甲基腺嘌呤在急性肺炎小鼠模型中,感染增强了不依赖自噬的存活,同时伴随着细菌负荷的减少、病理学的减轻和炎性细胞因子的减少。有趣的是,这些有益作用不依赖于嗜中性粒细胞募集或吞噬作用,而是依赖于通过抑制 3-MA 预处理嗜中性粒细胞的细胞死亡而诱导的杀伤能力增强。这些发现表明 3-MA 预处理对铜绿假单胞菌诱导的急性肺炎具有新的保护作用。