Rickettsia conorii infection of C3H/HeN mice. A model of endothelial-target rickettsiosis

Abstract

Background: Rickettsial diseases result from disseminated intraendothelial cell infection. The clinically critical conditions, meningoencephalitis and interstitial pneumonia, are associated with multifocal rickettsial vascular injury.

Experimental design: C3H/HeN mice inoculated intravenously with either 2.25 x 10(3) or 2.25 x 10(5) Rickettsia conorii (Malish 7 strain) were observed for illness with sacrifice of animals for evaluation of pathologic lesions and host responses by light and electron microscopy, rickettsial content and location by plaque assay, immunohistology, and electron microscopy, and immune response by cytokine analyses and serology.

Results: Mice inoculated with a high dose of rickettsiae established disseminated endothelial infection on day 1, became ill with progressive increase in rickettsiae on day 4, and died with vascular injury-based meningoencephalitis and interstitial pneumonia on day 5 or 6. Mice inoculated with the low rickettsial dose became ill on day 5 and recovered by day 10. Clearance of rickettsiae was associated with lymphohistiocytic perivasculitis. Rickettsial infection of Kupffer cells and hepatocytes led to the formation of transient hepatic granulomas. Infection-associated loss of the ability of spleen cells to secrete interleukin-2 on stimulation with concanavalin A suggested transient immunosuppression.

Conclusions: This experimental infection provides the best available model for rickettsial disease with endothelial infection and injury, immune rickettsial clearance, regeneration of endothelium, and repair of the vascular lesions.