Experimental pulmonary candidiasis in modified rabbits. Histopathological, ultrastructural and enzyme cytochemical studies of tissue reactions.

Abstract

The present experiment was performed in order to analyze and compare the histopathological features of Candida infection in various states of host defense capacity. The pulmonary lesions were induced by an intratracheal inoculation of 10(8) live cells of Candida albicans into each of the rabbits in the following 4 groups: 1) untreated controls, 2) animals sensitized non-specifically to bovine serum albumin (BSA), 3) those sensitized specifically to formalin-killed C. albicans cells, and 4) those treated with cyclophosphamide and mitomycin C. The animals were sacrificed at appropriate intervals up to 16 days after inoculation. At autopsy, the lungs were cultured and then subjected to histopathological, electron microscopic and enzyme cytochemical examinations. In the healthy control animals, the fungal lesions consisted of polymorphonuclear leukocytes (PMN) at the initial stage, gradually changing to granulomatous inflammation, which contained no peroxidase-positive macrophages. In the animals sensitized non-specifically to BSA exudative macrophages appeared in the lesions, the nature of which did not differ from that of the control animals. In the animals sensitized specifically to Candida cells, more extensive infiltration of PMN was observed at the initial stage, a fact which may suggest the participation of the Arthus phenomenon in the development of the lesions. Furthermore, an epithelioid cell transformation of the macrophages in the granulomatous lesions may also suggest that immune complexes contributed to their formation. In the drug-treated animals, the lesions consisted of necrotic or less prominent cellular foci which correspond to the features of human candidiasis in debilitated states, and the inoculated fungi grew progressively to form pseudohyphae. An asteroid structure protruding radially from the surface of the fungal cells and attaching to primary lysosomes in the phagocytes was observed occasionally. This structure seems to be formed when the function of the phagocytes in the defense mechanisms against the fungi is suppressed to some extent. From the results of the present experiment, we would emphasize that PMN play an initial role in the elimination of C. albicans cells in the lung, and that macrophages then contribute to the formation of the lesions immunologically or non-immunologically.