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To prevent and treat these complications, biomarkers and molecular mediators must be identified. Persistent immune reprogramming in the form of immunoparalysis and impaired host defense is proposed to mediate late pulmonary complications after sepsis, particularly new pulmonary infections. However, immune reprogramming may also involve enhanced\/primed responses to secondary stimuli, although their contribution to long-term sepsis complications remains understudied. We hypothesize that enhanced\/primed immune responses in the lungs of sepsis survivors are associated with late pulmonary complications. To this end, we developed a murine sepsis model using cecal ligation and puncture (CLP) followed 3\u2009wk later by administration of intranasal lipopolysaccharide to induce inflammatory lung injury. Mice surviving sepsis exhibit enhanced lung injury with increased alveolar permeability, neutrophil recruitment, and enhanced Ly6C<jats:sup>hi<\/jats:sup> monocyte Tnf expression. To determine the mediators of enhanced lung injury, we performed flow cytometry and RNA sequencing of lungs 3\u2009wk after CLP, prior to lipopolysaccharide. Sepsis survivor mice showed expanded Ly6C<jats:sup>hi<\/jats:sup> monocytes populations and increased expression of many inflammatory genes. Of these, S100A8\/A9 was also elevated in the circulation of human sepsis survivors for months after sepsis, validating our model and identifying S100A8\/A9 as a potential biomarker and therapeutic target for long-term pulmonary complications after sepsis. These data provide new insight into the importance of enhanced\/primed immune responses in survivors of sepsis and establish a foundation for additional investigation into the mechanisms mediating this response. <\/jats:p>","DOI":"10.1152\/ajplung.00123.2021","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T23:50:32Z","timestamp":1624492232000},"page":"L451-L465","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Long-term survivors of murine sepsis are predisposed to enhanced LPS-induced lung injury and proinflammatory immune reprogramming"],"prefix":"10.1152","volume":"321","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9173-5146","authenticated-orcid":true,"given":"Scott J.","family":"Denstaedt","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, 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