Infectious Agents in Immunodeficient Murine Models: Pathogenicity of Nocardia asteroides in Congenitally Athymic (Nude) and Hereditarily Asplenic (Dh/+) Mice

Abstract

Congenitally athymic (Nu/Nu), hereditarily asplenic (Dh/+), and littermate control mice were given intravenous injections of homogeneous cell suspensions of the virulent Nocardia asteroides GUH-2. Kill curve, 50% lethal dose, and kidney clearance data were obtained over a period of 3 months postinfection. N. asteroides initiated both an acute infectious process and a chronic, progressive disease in these animals when given intravenously. The heterozygous (Nu/+) mice appeared to be slightly more susceptible to the acute phase of infection than their nude littermates. In contrast, nude mice were at least 50 times more susceptible to chronic nocardial infection than were the heterozygous (Nu/+) controls. Swiss Webster specific pathogen-free mice were similar to heterozygous (Nu/+) mice in their susceptibility to N. asteroides. The hereditarily asplenic (Dh/+) mice were not as susceptible to lethal infection as were nude mice. However, asplenic mice demonstrated an inability to eliminate nocardia from infected kidneys, whereas their littermate control (+/+) mice were able to mount an effective response and destroy most of the organisms within the kidneys. Similar observations were noted when nude and heterozygous (Nu/+) littermate mice were infected in the footpad. The nude mice developed a systemic infection and died within 4 weeks with little inflammation of the footpad and no macroscopic lesions. In contrast, heterozygous (Nu/+) mice developed extensive local abscesses in the foot that persisted for at least 4 weeks. There was no animal death and no evidence of dissemination. The data presented herein indicate that T cells are essential for adequate host response against infection with a virulent strain of N. asteroides.