RICKETTSIA-AUSTRALIS INFECTION - A MURINE MODEL OF A HIGHLY INVASIVE VASCULOPATHIC RICKETTSIOSIS

A mouse model of spotted fever group rickettsiosis, in which disease r esults from disseminated rickettsial infection of endothelial cells an d vascular damage, was developed by intravenous inoculation of 6- to 8 -week-old, male, Balb/c mice with Rickettsia australis. Animals develo ped progressively severe vasculitis, interstitial pneumonia, and multi focal hepatic necrosis. These lesions correlated with early disseminat ed infection of endothelial cells followed by growth and invasion of r ickettsiae into perivascular cells. The dose of 2 x 10(6) organisms wa s uniformly lethal. Serum interleukin- (IL) 1, IL-6, and interferon (I FN) increased by day 3 and tumor necrosis factor (TNF) on day 5. TNF, IL-6, and IFN declined on day 7. Spleen cells responded to Rickettsia australis antigen by producing IFN, TNF, IL-1, and IL-6 on day 5, foll owed by lower quantities of these cytokines on day 7. Despite the prod uction of antibodies, IFN, TNF, IL-1, and IL-6, a lethal outcome occur red frequently. A decreased ability to secrete IL-2 suggests an elemen t Of infection-associated immunosuppression.