title: [Novel model of replicative Legionella pneumophila lung infection in DBA/2 mice].
abstract: We present here a new model of Legionella pneumophila lung infection in DBA/2 mice. By intranasal inoculation with 106 colony-forming units of L. pneumophila strain suzuki serogoup 1, persistent non-lethal lung infection was established as reflected by the detection of more than 10(4) CFU/lung of the organism 14 days after infection. Treatment of mice with cyclophosphamide before infection enhanced bacterial replication in the lungs and all cyclophosphamide-treated mice experienced lethal infection. Histopathologically, the course of non-lethal lung infection was characterized by early response of neutrophiles, then monocyte/macrophages response in the alveoli with disease progression, and diffuse alveolar wall thickening with lymphocyte migration at later phase of infection. Transmission electron microscopic evaluation of the lungs confirmed that L. pneumophila located intracellularly within neutrophiles and infrequently intracellular bacteria were observed undergoing binary fission. Therefore, the mouse model of replicative L. pneumophila lung infection provides method for evaluating pathogenesis of L. pneumophila lung infection and antibacterial therapy.
authors.affiliation: Daiichi Sankyo Co. Ltd., Biological Research Laboratories IV.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kashimoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kurosaka
authors.forename: Yukie
authors.initials: Y
authors.lastname: Karibe
authors.forename: Saori
authors.initials: S
authors.lastname: Uoyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Namba
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Otani
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D003520:Cyclophosphamide; D004195:Disease Models, Animal; D018450:Disease Progression; D016952:Legionella pneumophila / Q000254:growth & development; D007877:Legionnaires' Disease / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D008855:Microscopy, Electron, Scanning; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000382:microbiology
chemical_list: D003520:Cyclophosphamide