title: Injury enhances resistance to Escherichia coli infection by boosting innate immune system function.
abstract: Major injury is widely thought to predispose the injured host to opportunistic infections. This idea is supported by animal studies showing that major injury causes reduced resistance to polymicrobial sepsis induced by cecal ligation and puncture. Although cecal ligation and puncture represents a clinically relevant sepsis model, we wanted to test whether injury might also lead to greater susceptibility to peritoneal infection caused by a single common pathogen, Escherichia coli. Contrary to our expectation, we show herein that the LD(50) for sham-injured mice was 10(3) CFU of E. coli, whereas the LD(50) for burn-injured mice was 50 x 10(3) CFU at 7 days postinjury. This injury-associated enhanced resistance was apparent as early as 1 day after injury, and maximal resistance was observed at days 7 and 14. We found that burn-injured mice had higher numbers of circulating neutrophils and monocytes than did sham mice before infection and that injured mice were able to recruit greater numbers of neutrophils to the site of infection. Moreover, the peritoneal neutrophils in burn-injured mice were more highly activated than neutrophils from sham mice as determined by Mac-1 expression, superoxide generation, and bactericidal activity. Our findings suggest that the enhanced innate immune response that develops following injury, although it is commonly accepted as the mediator of the detrimental systemic inflammatory response syndrome, may also, in some cases, benefit the injured host by boosting innate immune antimicrobial defenses.
authors.affiliation: Department of Surgery (Immunology), Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Adrian A
authors.initials: AA
authors.lastname: Maung
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujimi
authors.forename: Malcolm P
authors.initials: MP
authors.lastname: MacConmara
authors.forename: Goro
authors.initials: G
authors.lastname: Tajima
authors.forename: Ann M
authors.initials: AM
authors.lastname: McKenna
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Delisle
authors.forename: Christopher
authors.initials: C
authors.lastname: Stallwood
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Onderdonk
authors.forename: John A
authors.initials: JA
authors.lastname: Mannick
authors.forename: James A
authors.initials: JA
authors.lastname: Lederer
mesh_terms: D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology / Q000382:microbiology; D002056:Burns / Q000276:immunology* / Q000382:microbiology* / Q000401:mortality; D004927:Escherichia coli Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008262:Macrophage Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation / Q000276:immunology; D009894:Opportunistic Infections / Q000276:immunology / Q000401:mortality / Q000517:prevention & control