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In this study, we established a model of intratracheal <jats:italic>Klebsiella pneumoniae<\/jats:italic> administration in young adult male and female mice, at 4 days following an experimental TBI, to investigate how <jats:italic>K. pneumoniae<\/jats:italic> infection influences acute post-TBI outcomes. A dose-response curve determined the optimal dose of <jats:italic>K. pneumoniae<\/jats:italic> for inoculation (1 x\u00a010^6 colony forming units), and administration at 4 days post-TBI resulted in transient body weight loss and sickness behaviors (hypoactivity and acute dyspnea). <jats:italic>K. pneumoniae<\/jats:italic> infection led to an increase in pro-inflammatory cytokines in serum and bronchoalveolar lavage fluid at 24\u00a0h post-infection, in both TBI and sham (uninjured) mice. By 7 days, when myeloperoxidase\u2009+\u2009neutrophil numbers had returned to baseline in all groups, lung histopathology was observed with an increase in airspace size in TBI\u2009+\u2009<jats:italic>K. pneumoniae<\/jats:italic> mice compared to TBI\u2009+\u2009vehicle mice. In the brain, increased neuroinflammatory gene expression was observed acutely in response to TBI, with an exacerbated increase in <jats:italic>Ccl2<\/jats:italic> and <jats:italic>Hmox1<\/jats:italic> in TBI\u2009+\u2009<jats:italic>K. pneumoniae<\/jats:italic> mice compared to either TBI or <jats:italic>K. pneumoniae<\/jats:italic> alone. However, the presence of neuroinflammatory immune cells in the injured brain, and the extent of damage to cortical and hippocampal brain tissue, was comparable between <jats:italic>K. pneumoniae<\/jats:italic> and vehicle-treated mice by 7 days. Examination of the fecal microbiome across a time course did not reveal any pronounced effects of either injury or <jats:italic>K. pneumoniae<\/jats:italic> on bacterial diversity or abundance. Together, these findings demonstrate that <jats:italic>K. pneumoniae<\/jats:italic> lung infection after TBI induces an acute and transient inflammatory response, primarily localized to the lungs with some systemic effects. However, this infection had minimal impact on secondary injury processes in the brain following TBI. Future studies are needed to evaluate the potential longer-term consequences of this dual-hit insult.<\/jats:p>","DOI":"10.1186\/s12974-024-03093-9","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T17:01:49Z","timestamp":1715187709000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Modelling lung infection with Klebsiella pneumoniae after murine traumatic brain injury"],"prefix":"10.1186","volume":"21","author":[{"given":"Ali","family":"Shad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah S. 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