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.

Relationship among cell wall composition, stage of growth, and virulence of Nocardia asteroides GUH-2

“…The mechanisms of virulence in N. asteroides GUH-2 are complex and"not completely understood (3,4,6,7,9,10,12).…”

“…At 3, 24, and 48 h after injection, five mice from each group were sacrificed by ether overdose. The brains, livers, lungs, kidneys, and spleens were removed and homogenized, and the bacteria in each organ were quantitated as described previously (6)(7)(8).…”

“…It was derived from the original isolate by serially selecting single-colony isolates. The pathogenesis of this organism has been studied extensively (3,4,(6)(7)(8)(9)(10). A cloned isolate of N. asteroides GUH-2P was grown to mid-log phase in brain heart infusion broth, a single-cell suspension was prepared in phosphate-buffered saline, and the cell concentration was adjusted to approximately 107 CFU/ml.…”

Adoptive transfer of immunity to Nocardia asteroides in nude mice

“…Congenitally athymic (nude) littermate mice (nu/nu) were used as recipients in adoptive transfer experiments. The nude and heterozygous littermates were maintained at the Animal Resource Service of the University of California as described previously (3). The genetic background of these mice has been described previously (13).…”

“…Likewise, T cells seem to be important in pulmonary clearance of N. asteroides, since congenitally athymic (nude) mice cannot eliminate the intranasally administered bacteria (5). In addition, nude mice are 50-fold more susceptible than heterozygous (nu/+) littermates to intravenous challenge with N. asteroides (3). Because these data suggest that T cells are critical during murine host resistance to nocardial infection, this study attempts to determine whether resistance to N. asteroides can be adoptively transferred to nude mice with T cells from unmanipulated versus Nocardia-immunized heterozygous (nu/+) littermates.…”