Histopathological and electron microscopical studies on experimental Penicillium marneffei infection in mice.

Experimental Penicillium marneffei infection in mice was investigated histopathologically and by electron microscopy. Viable conidia (5 x 10(6) cells) of P. marneffei were inoculated into each mouse of group A (BALB/c mice) and group B (BALB/c-nu/nu-SIc mice) through the tail vein. All the mice were sacrificed at intervals and the livers were examined. In group A, the conidia were phagocytosed by Kupffer cells soon after inoculation, and proliferated by fission in the cytoplasm. Marked proliferation of yeast cells was observed 7 and 14 days after inoculation. With proliferation of the fungus, the number of lysosomes in Kupffer cells increased, and numerous granulomas were formed in the liver. These granulomas consisted mainly of macrophages with yeast cells, together with a few polymorphonuclear leukocytes, lymphocytes and giant cells. From 28 days on yeast cells were gradually cleared from the granulomas, and 56 days after inoculation almost all the granulomas disappeared. In group B, at an early stage of infection, similar pathological changes to those seen in mice of group A were observed. However, as the infection progressed, the number of granulomas continued to increase and yeast cells continued to proliferate although lymphocytes did not infiltrate these granulomas. With proliferation of yeast cells the liver tissue was replaced with both yeast cells engulfed by macrophages and extracellular yeasts, and dissemination occurred.