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首页> 外文期刊>Infection and immunity >Distinct Contributions of Neutrophils and CCR2+ Monocytes to Pulmonary Clearance of Different Klebsiella pneumoniae Strains
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Distinct Contributions of Neutrophils and CCR2+ Monocytes to Pulmonary Clearance of Different Klebsiella pneumoniae Strains

机译：中性粒细胞和CCR2 +单核细胞对不同肺炎克雷伯菌肺炎清除率的不同贡献。

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Klebsiella pneumoniae is a common respiratory pathogen, with some strains having developed broad resistance to clinically available antibiotics. Humans can become infected with many different K. pneumoniae strains that vary in genetic background, antibiotic susceptibility, capsule composition, and mucoid phenotype. Genome comparisons have revealed differences between K. pneumoniae strains, but the impact of genomic variability on immune-mediated clearance of pneumonia remains unclear. Experimental studies of pneumonia in mice have used the rodent-adapted 43816 strain of K. pneumoniae and demonstrated that neutrophils are essential for optimal host defense. It remains unclear, however, whether CCR2+ monocytes contribute to K. pneumoniae clearance from the lung. We selectively depleted neutrophils, CCR2+ monocytes, or both from immunocompetent mice and determined susceptibility to infection by the 43816 strain and 4 newly isolated clinical K. pneumoniae strains. The clinical K. pneumoniae strains, including one carbapenem-resistant ST258 strain, are less virulent than 43816. Optimal clearance of each of the 5 strains required either neutrophils or CCR2+ monocytes. Selective neutrophil depletion markedly worsened infection with K. pneumoniae strain 43816 and three clinical isolates but did not increase susceptibility of mice to infection with the carbapenem-resistant K. pneumoniae ST258 strain. Depletion of CCR2+ monocytes delayed recovery from infection with each of the 5 K. pneumoniae strains, revealing a contribution of these cells to bacterial clearance from the lung. Our findings demonstrate strain-dependent variation in the contributions of neutrophils and CCR2+ monocytes to clearance of K. pneumoniae pulmonary infection.
机译：肺炎克雷伯菌是一种常见的呼吸道病原体，有些菌株对临床上可用的抗生素产生了广泛的耐药性。人类可能会感染许多不同的肺炎克雷伯氏菌菌株，这些菌株的遗传背景，抗生素敏感性，胶囊成分和黏液表型各不相同。基因组的比较揭示了肺炎克雷伯氏菌菌株之间的差异，但基因组变异性对免疫介导的肺炎清除的影响尚不清楚。小鼠肺炎的实验研究使用了适应啮齿动物的肺炎克雷伯菌43816菌株，并证明中性粒细胞对于最佳宿主防御至关重要。然而，尚不清楚CCR2 +单核细胞是否有助于肺炎克雷伯菌从肺部清除。我们从具有免疫能力的小鼠中选择性地去除了中性粒细胞，CCR2 +单核细胞或两者，并确定了43816株和4种新近分离出的临床肺炎克雷伯菌菌株对感染的敏感性。临床上的肺炎克雷伯菌菌株（包括一株对碳青霉烯耐药的ST258菌株）的毒性低于43816。这5株菌株的最佳清除需要嗜中性粒细胞或CCR2 +单核细胞。选择性中性粒细胞耗竭显着加剧了肺炎克雷伯菌菌株43816和三种临床分离株的感染，但并未增加小鼠对耐碳青霉菌抗性肺炎克雷伯菌ST258菌株感染的敏感性。 CCR2 +单核细胞的耗竭延迟了感染5株肺炎克雷伯菌每株的恢复，揭示了这些细胞对从肺中清除细菌的贡献。我们的发现表明嗜中性粒细胞和CCR2 +单核细胞清除肺炎克雷伯菌肺部感染的作用与菌株有关。

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