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Cryptococcus neoformans: a central nervous system isolate from an AIDS patient that is rhinotropic in a normal mouse
R A Fromtling1, G K Abruzzo, A Ruiz
1Department of Basic Microbiology, Merck Institute for Therapeutic Research, Rahway, NJ 07065-0900.
Abstract:
A strain of Cryptococcus neoformans that was isolated from the cerebrospinal fluid of a human diagnosed as having acquired immunodeficiency syndrome (AIDS), and that produced cutaneous lesions in experimentally infected, normal mice is described. Although no unusual cutaneous manifestations were noted in the patient's records, this isolate of C. neoformans proved to be dermotropic when injected intravenously into CD-1 mice. The LD50 at 28 days post infection ranged from 3.6-7.5 X 10(5) cells per mouse, and in vitro growth rate studies demonstrated that this isolate grew well at 35 degrees C and at 37 degrees C, but did not grow at 40 degrees C and higher. This isolate was rhinotropic producing large granulomatous lesions in the nasal tissues. Other cutaneous tissues affected were the periocular tissues, ears, feet and tail, although the granulomas were nodular in structure and less necrotic than the nasal lesions. The brain, lungs, liver, kidneys and spleen also were culture positive for C. neoformans. Histopathologically, each affected tissue examined had large densities of yeast cells and a chronic, granulomatous host response. Animals surviving the infection appeared to develop a commensal-type relationship with the infective yeast. This is the first report of an isolate of C. neoformans from an AIDS patient that has caused cutaneous manifestations in an animal model. The model described in this report may be useful for elucidating pathogenic mechanisms of cryptococcosis, particularly cutaneous manifestations of the disease.
Insights
This study describes a Cryptococcus neoformans strain from an AIDS patient that caused skin lesions in mice. This new animal model helps understand cryptococcosis, especially skin manifestations.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Cryptococcus neoformans is an opportunistic fungal pathogen.
- Acquired immunodeficiency syndrome (AIDS) increases susceptibility to cryptococcosis.
- Cutaneous manifestations of cryptococcosis are not well understood in animal models.
Purpose of the Study:
- To describe a novel Cryptococcus neoformans isolate from an AIDS patient.
- To characterize the dermotropic and rhinotropic properties of this isolate in a mouse model.
- To establish an animal model for studying cryptococcal pathogenesis, particularly cutaneous disease.
Main Methods:
- Isolation of Cryptococcus neoformans from cerebrospinal fluid of an AIDS patient.
- Intravenous injection of the isolate into CD-1 mice.
- Assessment of lethality (LD50), in vitro growth rates, and histopathological examination of infected tissues.
- Evaluation of clinical signs and gross pathology.
Main Results:
- The isolate caused cutaneous lesions in experimentally infected mice, indicating dermotropism.
- The median lethal dose (LD50) was between 3.6-7.5 X 10(5) cells per mouse.
- Significant granulomatous lesions were observed in nasal tissues (rhinotropism), periocular areas, ears, feet, and tail.
- The fungus was also found in the brain, lungs, liver, kidneys, and spleen.
- Histopathology revealed high yeast cell densities and a chronic granulomatous host response in affected tissues.
- Surviving animals developed a commensal-like relationship with the yeast.
Conclusions:
- This is the first report of a Cryptococcus neoformans isolate from an AIDS patient causing cutaneous manifestations in an animal model.
- The described mouse model is valuable for elucidating pathogenic mechanisms of cryptococcosis, especially skin involvement.
- Further research using this model can advance understanding of cryptococcal virulence factors and host-pathogen interactions in cutaneous disease.