Interaction of Nocardia asteroides with Rabbit Alveolar Macrophages: Association of Virulence, Viability, Ultrastructural Damage, and Phagosome-Lysosome Fusion

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Abstract
In vitro-maintained rabbit alveolar macrophages were infected with 3 strains of N. asteroides. N. asteroides GUH-2 was resistant to macrophage killing, while N. asteroides 14759 was intermediate in resistance and N. asteroides 10905 had little resistance to killing by macrophages. These observations correlated well with the data on relative virulence previously determined in mice. To establish the intracellular events leading to these differences, the occurrence of phagosome-lysosome fusion in infected macrophages was determined by EM and fluorescent microscopic methods. The virulent strain GUH-2 inhibited phagosome-lysosome fusion; the intermediately virulent strain, 14759, partially inhibited fusion; and the less-virulent strain, 10905, was unable to inhibit fusion. EM of infected macrophages demonstrated that cells of the virulent strain, GUH-2, were not damaged and only some of the cells of the intermediately virulent strain, 14759, were damaged, while most of the cells of the less virulent strain, 10905, exhibited considerable cellular destruction. The virulence of these organisms was apparently correlated with their resistance to killing by alveolar macrophages, their lack of macrophage-induced ultrastructural damage and their ability to inhibit phagosome-lysosome fusion. Inhibition of phagosome-lysosome fusion in alveolar macrophages may be 1 mechanism of pathogenicity of virulent strains of N. asteroides.