title: Gene expression profiles of immune mediators and histopathological findings in animal models of leptospirosis: comparison between susceptible hamsters and resistant mice.
abstract: Leptospirosis is a widespread zoonosis characterized by multiple organ failure and variable host susceptibility toward pathogenic Leptospira strains. In this study, we put the role of inflammatory mediators in parallel with bacterial burdens and organ lesions by comparing a susceptible animal model, the hamster, and a resistant one, the Oncins France 1 (OF1) mouse, both infected with virulent Leptospira interrogans serovar Icterohaemorrhagiae strain Verdun. Histological observations evidenced edema, congestion, hemorrhage, and inflammatory infiltration in the organs of hamsters, in contrast to limited changes in mice. Using reverse transcription-quantitative PCR techniques, we showed that the relative Leptospira burden progressively increased in hamster tissues, while a rapid clearance was observed in mouse tissues. The early regulation of the proinflammatory mediators interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, and cyclo-oxygenase-2 and the chemokines gamma interferon-inducible protein 10 kDa/CXCL10 and macrophage inflammatory protein-1α/CCL3 in mouse tissues contrasted with their delayed and massive overexpression in hamster tissues. Conversely, the induction of the anti-inflammatory cytokine IL-10 was faster in the resistant than in the susceptible animal model. The role of these cytokines in the pathophysiology of leptospirosis and the implications of their differential regulation in the development of this disease are discussed.
authors.affiliation: Institut Pasteur de Nouvelle-Calédonie, Institut Pasteur International Network, Bacterial Research Laboratory, 9-11 Avenue Paul Doumer, BP 61, Noumea 98845, New Caledonia.
authors.forename: Mariko
authors.initials: M
authors.lastname: Matsui
authors.forename: Vincent
authors.initials: V
authors.lastname: Rouleau
authors.forename: Lilian
authors.initials: L
authors.lastname: Bruyère-Ostells
authors.forename: Cyrille
authors.initials: C
authors.lastname: Goarant
mesh_terms: D000818:Animals; D006224:Cricetinae; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D007668:Kidney / Q000473:pathology; D041383:Leptospira interrogans serovar icterohaemorrhagiae / Q000276:immunology*; D007922:Leptospirosis / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008647:Mesocricetus; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D012333:RNA, Messenger