title: Murine pulmonary infection and inflammation induced by inhalation of Burkholderia pseudomallei.
abstract: Melioidosis is a tropical disease caused by ingestion, percutaneous inoculation or inhalation of the Gram-negative soil saprophyte Burkholderia pseudomallei. We developed a reproducible experimental murine model of pneumonic melioidosis induced by inhalation of aerosolized B. pseudomallei 1026b. In a series of experiments performed to bracket the lethal dose, we found that C57BL/6 mice were modestly more resistant than BALB/c mice (median lethal dose 334 CFU/lung vs 204 CFU/lung). We further characterized infection and pulmonary inflammation in C57BL/6 mice infected with a sublethal dose. We observed pulmonary replication and dissemination of bacteria to distant organs in the first days after infection, followed by bacterial containment by day 4 and no evidence of recrudescent infection for up to 2 months. We measured a robust host inflammatory response notable for a neutrophilic bronchoalveolar lavage fluid profile, elevated cytokines and chemokines in the lung and serum and scattered foci of neutrophilic infiltrates in the alveoli and in a perivascular distribution on histological analysis. We previously noted a similar pattern of inflammation in mice infected with aerosolized B. thailandensis. This report builds on the limited literature describing experimental murine pneumonic melioidosis induced by aerosol and characterizes pulmonary infection and resultant inflammation in C57BL/6 mice infected with aerosolized B. pseudomallei. This model has utility for the study of bacterial and host factors that contribute to the virulence of melioidosis.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, WA 98104-2499, USA. tewest@uw.edu
authors.forename: T Eoin
authors.initials: TE
authors.lastname: West
authors.forename: Nicolle D
authors.initials: ND
authors.lastname: Myers
authors.forename: H Denny
authors.initials: HD
authors.lastname: Liggitt
authors.forename: Shawn J
authors.initials: SJ
authors.lastname: Skerrett
mesh_terms: D000336:Aerosols; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016957:Burkholderia pseudomallei / Q000472:pathogenicity / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019570:Inhalation Exposure / Q000009:adverse effects; D008136:Longevity; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008554:Melioidosis / Q000378:metabolism / Q000382:microbiology* / Q000401:mortality; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology; D018410:Pneumonia, Bacterial / Q000378:metabolism / Q000382:microbiology* / Q000401:mortality; D013047:Specific Pathogen-Free Organisms; D015996:Survival Rate
chemical_list: D000336:Aerosols; D015415:Biomarkers; D016207:Cytokines