title: Understanding the host inflammatory response to wound infection: an in vivo study of Klebsiella pneumoniae in a rabbit ear wound model.
abstract: Wound infection development is critically dependent on the complex interactions between bacteria and host. Klebsiella pneumoniae has become an increasingly common wound pathogen, but its natural history within wounds has never been studied. Using a validated, in vivo rabbit ear model, wounds were inoculated with K. pneumoniae at different concentrations (10²-10⁷ colony-forming units) with measurement of viable and nonviable bacterial counts, histological wound-healing parameters, and host inflammatory gene expression at multiple time points postinoculation (48, 96, and 240 hours). Bacteria and wound morphologies were evaluated with scanning electron microscopy. Comparable experiments were performed in ischemic ears to model immune response impairment. All wounds, despite different inoculants, equilibrated to similar bacterial concentrations by 96 hours. With a 10⁶ colony-forming units inoculant, wounds at 240 hours showed decreased bacterial counts (p < 0.01), with a corresponding improvement in healing (p < 0.01) and a decrease in inflammatory response (p < 0.05). In contrast, ischemic wounds revealed impaired inflammatory gene expression (p < 0.05) resulting in higher steady-state bacterial concentrations (p < 0.01), impaired healing (p < 0.05), and biofilm formation on scanning electron microscopy. We conclude that a normal inflammatory response can effectively stabilize and overcome a K. pneumoniae wound infection. An impaired host cannot control this bacterial burden, preventing adequate healing while allowing bacteria to establish a chronic presence. Our novel study quantitatively validates the host immune response as integral to wound infection dynamics.
authors.affiliation: Division of Plastic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Akhil K
authors.initials: AK
authors.lastname: Seth
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Geringer
authors.forename: Anandev N
authors.initials: AN
authors.lastname: Gurjala
authors.forename: Johnathan A
authors.initials: JA
authors.lastname: Abercrombie
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: You
authors.forename: Seok J
authors.initials: SJ
authors.lastname: Hong
authors.forename: Robert D
authors.initials: RD
authors.lastname: Galiano
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Mustoe
authors.forename: Kai P
authors.initials: KP
authors.lastname: Leung
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004423:Ear / Q000293:injuries / Q000382:microbiology* / Q000473:pathology; D007249:Inflammation; D007511:Ischemia / Q000382:microbiology* / Q000503:physiopathology; D007710:Klebsiella Infections / Q000382:microbiology* / Q000503:physiopathology; D007711:Klebsiella pneumoniae / Q000472:pathogenicity*; D012333:RNA, Messenger; D011817:Rabbits; D013234:Stem Cells; D014945:Wound Healing; D014946:Wound Infection / Q000382:microbiology* / Q000503:physiopathology
chemical_list: D012333:RNA, Messenger