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Host defense against experimental paracoccidioidomycosis
Abstract:
An experimental model for the study of paracoccidioidomycosis was established in BALB/c mice. Both normal and athymic nu/nu animals were challenged intraperitoneally and intratracheally with yeastlike cells of Paracoccidioides brasiliensis. After challenge, all immunologically intact (+/+) mice survived, whereas nu/nu mice gradually succumbed. The latter had focal peritoneal, liver, spleen, and lung lesions consisting of P. brasiliensis with inflammation, polymorphonuclear leukocytes, monocytes, and histiocytic reactions, but no granuloma formation. Thymus transplantation heightened resistance of nu/nu mice to P. brasiliensis. These studies indicate that the nu/nu mouse develops progressive lethal paracoccidioidomycosis after intraperitoneal and intratracheal challenge, and that thymus-dependent immune mechanisms mediate host defense.
Insights
Athymic nu/nu mice developed lethal paracoccidioidomycosis after infection with Paracoccidioides brasiliensis, while normal mice survived. This highlights the critical role of thymus-dependent immunity in controlling this fungal infection.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Paracoccidioidomycosis is a systemic fungal infection endemic in Latin America.
- The role of T-cell mediated immunity in controlling Paracoccidioides brasiliensis infection is not fully understood.
Purpose of the Study:
- To establish an experimental model for studying paracoccidioidomycosis in mice.
- To investigate the role of thymus-dependent immunity in host defense against P. brasiliensis.
Main Methods:
- BALB/c mice, both normal (+/+) and athymic (nu/nu), were infected with P. brasiliensis via intraperitoneal and intratracheal routes.
- Lesion development, survival rates, and inflammatory responses were monitored.
- Thymus transplantation was performed in nu/nu mice to assess its effect on resistance.
Main Results:
- Athymic nu/nu mice succumbed to progressive, lethal paracoccidioidomycosis, exhibiting disseminated lesions in the peritoneum, liver, spleen, and lungs.
- Lesions in nu/nu mice showed P. brasiliensis, inflammation, and various immune cells but lacked granuloma formation.
- Immunologically intact (+/+) mice survived the infection.
- Thymus transplantation significantly enhanced the resistance of nu/nu mice to P. brasiliensis.
Conclusions:
- The nu/nu mouse model is susceptible to progressive lethal paracoccidioidomycosis, making it suitable for studying the disease.
- Thymus-dependent immune mechanisms are crucial for mediating host defense and controlling P. brasiliensis infection.
- Understanding these immune mechanisms can inform therapeutic strategies for paracoccidioidomycosis.
