The nocardiae are bacteria belonging to the aerobic actinomycetes. They are an important part of the normal soil microflora worldwide. The type species, Nocardia asteroides, and N. brasiliensis, N. farcinica, N. otitidiscaviarum, N. nova, and N. transvalensis cause a variety of diseases in both normal and immunocompromised humans and animals. The mechanisms of pathogenesis are complex, not fully understood, and include the capacity to evade or neutralize the myriad microbicidal activities of the host. The relative virulence of N. asteroides correlates with the ability to inhibit phagosome-lysosome fusion in phagocytes; to neutralize phagosomal acidification; to detoxify the microbicidal products of oxidative metabolism; to modify phagocyte function; to grow within phagocytic cells; and to attach to, penetrate, and grow within host cells. Both activated macrophages and immunologically specific T lymphocytes constitute the major mechanisms for host resistance to nocardial infection, whereas B lymphocytes and humoral immunity do not appear to be as important in protecting the host. Thus, the nocardiae are facultative intracellular pathogens that can persist within the host, probably in a cryptic form (L-form), for life. Silent invasion of brain cells by some Nocardia strains can induce neurodegeneration in experimental animals; however, the role of nocardiae in neurodegenerative diseases in humans needs to be investigated.

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The roles of nocardial superoxide dismutase (SOD) and catalase in the resistance of Nocardia asteroides to the microbicidal properties of human polymorphonuclear leukocytes were determined in vitro. The neutrophils killed ca. 80% of the cells of the less virulent N. asteroides 10905 and ca. 50% of the log phase of the more virulent N. asteroides GUH-2 after 180 min of incubation. These phagocytes were not able to kill earlystationary-phase cells of strain GUH-2 that contained 10 times more intracytoplasmic catalase than log-phase cells of the same culture. However, the polymorphonuclear leukocytes were able to kill more than 50% of the cells of early-stationary-phase strain GUH-2 after treatment with purified antibody specific for surface-associated SOD. No killing was observed when the bacteria were treated with normal rabbit immunoglobulin G or with serum obtained from rabbits immunized against whole nocardial cells (containing little or no activity against SOD). These phagocytes killed more than 99% of Listeria monocytogenes used as a control. Chlorpromazine-treated polymorphonuclear leukocytes killed L. monocytogenes (70%) but they were not able to kill antibody-treated cells of N. asteroides GUH-2. Exogenously added SOD partially protected strain 10905, which lacked surface-associated enzyme, but it had no effect on the killing of strain GUH-2, which already possessed significant amounts of surface-bound SOD. In contrast, catalase added to the nocardiae provided almost complete protection to the log-phase cells of strain GUH-2, but strain 10905 was only partially protected. SOD combined with catalase had additive activity which completely protected the cells of strain 10905. A mutant of N. asteroides GUH-2 (SCII-C) is more virulent during the log phase than is the parental strain. This mutant contained at least 7 times more catalase at this stage of growth than did the parent. No other differences between these two strains were observed during the log phase. In sharp contrast to those of the parent, log-phase cells of this high-catalase mutant were not killed by polymorphonuclear phagocytes. These data indicate a role for both SOD and catalase in the resistance of Nocardia spp. to human neutrophils, and they represent at least two factors associated with virulence.

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Previously, it was shown that arthroconidia of Coccidioides immitis appear to inhibit phagosome-lysosome fusion and survive within normal mouse peritoneal macrophages. However, when these macrophages are exposed to antigen-stimulated T lymphocytes from immune mice, activation occurs, leading to enhanced phagosome-lysosome fusion and killing of C. immitis. Results indicate that the activation of macrophages can be effected after incubation with soluble lymphocyte product(s) (lymphokines). The activation of macrophages results if the macrophages are exposed to the lymphokine before, but not after, infection. The results indicate that the lymphocyte population responsible for the elaboration of the lymphokine is phenotypically Lytl 2-and that activation of macrophages by the lymphokine can occur across H-2 histocompatibility barriers.