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
{"title":"铜绿假单胞菌肺部感染导致S100A8/A9依赖性心脏功能障碍。","authors":"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","doi":"10.1371/journal.ppat.1011573","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20178,"journal":{"name":"PLoS Pathogens","volume":null,"pages":null},"PeriodicalIF":6.7000,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484443/pdf/","citationCount":"0","resultStr":"{\"title\":\"Pseudomonas aeruginosa pulmonary infection results in S100A8/A9-dependent cardiac dysfunction.\",\"authors\":\"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\",\"doi\":\"10.1371/journal.ppat.1011573\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":20178,\"journal\":{\"name\":\"PLoS Pathogens\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2023-08-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484443/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"PLoS Pathogens\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1371/journal.ppat.1011573\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/8/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"Immunology and Microbiology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"PLoS Pathogens","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1371/journal.ppat.1011573","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"Immunology and Microbiology","Score":null,"Total":0}
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.
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.