铜绿假单胞菌肺部感染导致S100A8/A9依赖性心脏功能障碍。

IF 6.7 1区 医学 Q1 Immunology and Microbiology
PLoS Pathogens Pub Date : 2023-08-25 eCollection Date: 2023-08-01 DOI:10.1371/journal.ppat.1011573
Naresh Kumar, Matthew J Pestrak, Qian Wu, Omar Santiagonunez Ahumada, Sheri Dellos-Nolan, Noushin Saljoughian, Rajni Kant Shukla, Cortney F Mitchem, Prabhakara R Nagareddy, Latha P Ganesan, Lafuse P William, Daniel J Wozniak, Murugesan V S Rajaram
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引用次数: 0

摘要

铜绿假单胞菌(P.a.)感染占所有医院获得性肺炎病例的近20%,死亡率>30%。P.a.感染可诱导强烈的炎症反应,理想情况下可增强细菌清除率。不幸的是,过度炎症也会产生负面影响,并经常导致心脏功能障碍和相关的发病率和死亡率。然而,目前尚不清楚P.a.肺部感染是如何导致心脏功能障碍的。使用小鼠肺炎模型,我们发现肺部P.a.感染会导致严重的心脏左心室功能障碍和电异常。更具体地说,我们发现肺中S100A8/A9的中性粒细胞募集和释放激活TLR4/RAGE信号通路,进而增强全身炎症和随后的心脏功能障碍。矛盾的是,S100A8/A9的整体缺失并没有改善,但加剧了心脏功能障碍和死亡率,这可能是由于肺部和心脏中的细菌负担不受控制。我们的研究结果表明,P.a.感染诱导的S100A8/9的释放是一把双刃剑,增加了心脏功能障碍的风险,但限制了P.a.的生长。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pseudomonas aeruginosa pulmonary infection results in S100A8/A9-dependent cardiac dysfunction.

Pseudomonas aeruginosa (P.a.) infection accounts for nearly 20% of all cases of hospital acquired pneumonia with mortality rates >30%. P.a. infection induces a robust inflammatory response, which ideally enhances bacterial clearance. Unfortunately, excessive inflammation can also have negative effects, and often leads to cardiac dysfunction with associated morbidity and mortality. However, it remains unclear how P.a. lung infection causes cardiac dysfunction. Using a murine pneumonia model, we found that P.a. infection of the lungs led to severe cardiac left ventricular dysfunction and electrical abnormalities. More specifically, we found that neutrophil recruitment and release of S100A8/A9 in the lungs activates the TLR4/RAGE signaling pathways, which in turn enhance systemic inflammation and subsequent cardiac dysfunction. Paradoxically, global deletion of S100A8/A9 did not improve but aggravated cardiac dysfunction and mortality likely due to uncontrolled bacterial burden in the lungs and heart. Our results indicate that P.a. infection induced release of S100A8/9 is double-edged, providing increased risk for cardiac dysfunction yet limiting P.a. growth.

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来源期刊
PLoS Pathogens
PLoS Pathogens 生物-病毒学
CiteScore
11.40
自引率
3.00%
发文量
598
审稿时长
2 months
期刊介绍: Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.
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