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Histopathological and electron microscopical studies on experimental Penicillium marneffei infection in mice
1Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Japan.
Abstract:
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.
Insights
Penicillium marneffei infection in mice causes yeast cell proliferation within Kupffer cells, forming granulomas. Immunocompetent mice clear the infection, while immunodeficient mice show uncontrolled fungal growth and dissemination.
Area of Science:
- Mycology
- Immunology
- Pathology
Background:
- Penicillium marneffei is an emerging fungal pathogen causing endemic mycosis in Southeast Asia.
- Understanding the host-pathogen interaction is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the histopathological and ultrastructural changes in the liver during experimental Penicillium marneffei infection in mice.
- To compare the disease progression in immunocompetent (BALB/c) and immunodeficient (BALB/c-nu/nu-SIc) mouse models.
Main Methods:
- Experimental infection of mice with viable Penicillium marneffei conidia via tail vein injection.
- Histopathological examination and electron microscopy of liver tissues at various time points post-inoculation.
- Assessment of fungal load, granuloma formation, and immune cell infiltration.
Main Results:
- In BALB/c mice, P. marneffei conidia were phagocytosed by Kupffer cells, proliferated as yeast cells, and induced granuloma formation. Granulomas resolved by 56 days post-infection.
- In BALB/c-nu/nu-SIc mice, fungal proliferation and granuloma formation were progressive, with limited lymphocyte infiltration and eventual liver tissue replacement and dissemination.
Conclusions:
- BALB/c mice demonstrate an effective immune response leading to clearance of P. marneffei infection.
- BALB/c-nu/nu-SIc mice are susceptible to disseminated P. marneffei infection, highlighting the role of T-cell mediated immunity in controlling the fungal burden.