Nocardia asteroides and Nocardia brasiliensis infections in mice

Abstract

A model for Nocardia asteroides and Nocardia brasiliensis infections in Swiss white mice has been established without the addition to the inocula of any form of adjuvant. Serial histopathological studies revealed that these two actinomycetes cause lesions that are quite different in their features. An acute suppurative abscess characterizes the lesions of N. asteroides. In the case of N. brasiliensis infections a granuloma is produced in which a striking feature is the presence of large numbers of foam-laden macrophages, although occasional exceptions to this pattern were noted. Electron microscopic studies demonstrated that these macrophages contain within their cytoplasm organisms in varying stages of degeneration. Repeated mortality studies in mice failed to demonstrate differences in mortality rates produced by N. asteroides and N. brasiliensis. Thus, despite relatively trivial biochemical and antigenic differences between these two species of Nocardia, the local pathogenic response is quite different. The presence in the "brasiliensis lesion" of foamy macrophages with intracellular organisms is reminiscent of the histopathological features of lepromatous leprosy and of disseminated Myocobacterium bovis infection when this occurs in the immune suppressed situation. It is possible that N. brasiliensis infection produces a depression of cellular immunity that modifies the local host response to the organism.

Nocardia infections in congenitally athymic (nude) mice and in other inbred mouse strains

“…The loss of the ability of nude mice to produce a granuloma in response to N. brasiliensis suggests that the T-lymphocyte has a central role in the development of the granuloma. The results obtained in the C57/BL/6J, NZB, ICR, BALB/c, CBA/LAC, and C3H/eB mice indicate that other genetic factors do not influence the pathological picture that we have described previously for Swiss white mice (6).…”

“…6). The ultimate fate of these organisms could not be determined, but it appeared to be the same as that already shown in N. brasiliensis infection in Swiss white mice (6). DISCUSSION These findings demonstrate that there is an altered natural history and mortality produced by both N. asteroides and N. brasiliensis in congenitally athymic (nude) mice, c:mpared with Swiss white mice and the other inbred strains examined.…”

“…Congenitally athymic (nude) mice of both ICR and C3H/eB origins, and their normal littermates, and ICR, C57/BL/6J, NZB, BALB/c, CBA/LAC, and C3H/eB mice, weighing between 25 and 30 g, were obtained from the Veterinary Department, Weizmann Institute, Rehovot, Israel. Inoculations. The mice were inoculated intraperitoneally in the manner we described previously (6). Pathological studies.…”

“…These experiments were repeated in an identical manner with inoculations of N. brasiliensis. Routine staining of the histological sections and postmortem bacteriological examinations were performed as we described previously (6).…”

“…Nocardia infections in humans are becoming increasingly common after transplantation surgery (1, 10) and in patients whose normal immunity has been undermined by immunosuppressive drug therapy (5,11). The precise mechanisms by which nocardiosis develops in these situations have not been defined, although there is some evidence to suggest that disorders of cell-mediated immunity may be of particular importance in the pathogenesis of these infections (6,10,11).…”