title: Divergent role of gamma interferon in a murine model of pulmonary versus systemic Klebsiella pneumoniae infection.
abstract: Klebsiella pneumoniae is a leading cause of both community-acquired and nosocomial gram-negative-bacterial pneumonia. A further clinical complication of pulmonary K. pneumoniae infection is dissemination of bacteria from the lung into the peripheral blood, resulting in bacteremia concurrent with the localized pulmonary infection. Here, we report studies detailing the divergent role of gamma interferon (IFN-gamma) in pulmonary versus systemic K. pneumoniae infection. Intratracheal inoculation of IFN-gamma knockout mice resulted in significantly increased mortality compared to that observed for wild-type infected animals. Increased mortality correlated with a 100-fold increase in pulmonary bacteria within 2 days postinfection and upregulation of lung-associated interleukin-10 (IL-10) mRNA. Interestingly, IFN-gamma knockout mice had a twofold reduction in plasma aminospartate transferase activity, indicating diminished liver injury following peripheral blood bacterial dissemination. To study the host response towards blood-borne bacteria in the absence of the ongoing pulmonary infection, intravenous inoculation studies were initiated. IFN-gamma knockout mice were no more susceptible to intravenous infection than their wild-type counterparts. The consistent observation in IFN-gamma knockout mice was for improved survival correlating with increased clearance of blood- and liver-associated bacteria. Intravenous inoculation resulted in a two- to threefold increase in hepatic IL-10 production 24 and 48 h postinfection. Liver injury was also significantly reduced in IFN-gamma knockout mice. These data indicate that IFN-gamma secretion is a critical mediator in the resolution of localized gram-negative pulmonary pneumonia. Surprisingly, host responses towards systemic infection with the same bacteria appear to be IFN-gamma independent.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA. tmoore@umich.edu
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Moore
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Perry
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Getsoian
authors.forename: Michael W
authors.initials: MW
authors.lastname: Newstead
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Standiford
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000502:physiology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D007710:Klebsiella Infections / Q000276:immunology* / Q000473:pathology; D007711:Klebsiella pneumoniae; D008099:Liver / Q000473:pathology; D008171:Lung Diseases / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma