Gene expression profiles of immune mediators and histopathological findings in animal models of leptospirosis: comparison between susceptible hamsters and resistant mice

Infect Immun. 2011 Nov;79(11):4480-92. doi: 10.1128/IAI.05727-11. Epub 2011 Aug 15.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cricetinae
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Susceptibility
  • Gene Expression Profiling*
  • Gene Expression Regulation / immunology
  • Kidney / pathology
  • Leptospira interrogans serovar icterohaemorrhagiae / immunology*
  • Leptospirosis / immunology*
  • Leptospirosis / mortality
  • Leptospirosis / pathology*
  • Liver / pathology
  • Lung / pathology
  • Mesocricetus
  • Mice
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Cytokines
  • RNA, Messenger