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Unfortunately, excessive inflammation can also have negative effects, and often leads to cardiac dysfunction with associated morbidity and mortality. However, it remains unclear how\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>a<\/jats:italic>\n                    . lung infection causes cardiac dysfunction. Using a murine pneumonia model, we found that\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>a<\/jats:italic>\n                    . 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\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>a<\/jats:italic>\n                    . infection induced release of S100A8\/9 is double-edged, providing increased risk for cardiac dysfunction yet limiting\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>a<\/jats:italic>\n                    . growth.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011573","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T13:36:00Z","timestamp":1692970560000},"page":"e1011573","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Pseudomonas aeruginosa pulmonary infection results in S100A8\/A9-dependent cardiac dysfunction"],"prefix":"10.1371","volume":"19","author":[{"given":"Naresh","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Pestrak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar Santiagonunez","family":"Ahumada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheri","family":"Dellos-Nolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noushin","family":"Saljoughian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajni Kant","family":"Shukla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cortney F.","family":"Mitchem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhakara R.","family":"Nagareddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latha P.","family":"Ganesan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lafuse P.","family":"William","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Wozniak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1515-1122","authenticated-orcid":true,"given":"Murugesan V. 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