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Fibrosis patterns of lesions developed by athymic and euthymic mice infected with Paracoccidioides brasiliensis
H L Lenzi1, V L Calich, M Miyaji
1Departamento de Patologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brasil.
Abstract:
Athymic and euthymic mice with BALB/c background were used to study the patterns of fibrosis during ip infection with a virulent isolate of Paracoccidioides brasiliensis. Specimens from various organs were collected from the animals at 1, 4 and 7 weeks after infection and observed under light microscopy using various histologic staining methods. Lesions from the first week of infection, in both animal groups, presented a predominance of collagen III over I, carboxylated proteoglycans, and a tendency to encapsulation. From 4 weeks onward, the lesions of nu/+ mice tended to involute to macrophage-pseudoxanthomatous aggregates or to encapsulation with an increase of collagen I and sulfated proteoglycans. On the contrary, with the evolution of the infection, the nu/nu mice displayed permanently active lesions, rich in reticular fibers and carboxylated proteoglycans, with varied amounts of collagens III and I, without or with minimal encapsulation. However, independent of the type of mice, or of the type of lesions, the minimal P. brasiliensis-ECM unit was formed by a fibrillar cocoon of reticular fibers that encloses an individual yeast or a "family" composed of a mother cell plus one or various peripheral daughter cells, alone or engulfed by macrophages or giant cells. The overall difference of the lesions of nude and normal mice was not in isolated aspects of their components, but in the general architecture of the lesions. Those of nu/+ mice were either of involutive or of encapsulated type (slightly active), and those of nu/nu mice were of the sustained-expansive type (very active), without or with minimal encapsulation.
Insights
Athymic (nude) and euthymic (normal) mice infected with Paracoccidioides brasiliensis showed distinct fibrosis patterns. Nude mice developed sustained, active lesions, while normal mice exhibited involutive or encapsulated lesions, differing in overall lesion architecture.
Area of Science:
- Medical Mycology
- Immunology
- Pathology
Background:
- Paracoccidioides brasiliensis is a fungus causing paracoccidioidomycosis.
- The role of the host immune system, particularly T-cell mediated immunity, in controlling fungal infections is crucial.
- Fibrosis and extracellular matrix (ECM) remodeling are key features of chronic inflammatory diseases.
Purpose of the Study:
- To investigate the distinct patterns of fibrosis and extracellular matrix (ECM) deposition during Paracoccidioides brasiliensis infection in athymic (nude) versus euthymic (normal) mice.
- To characterize the temporal evolution of inflammatory lesions and their architectural differences in mice lacking T-cells.
- To understand the interplay between fungal burden, host immune response, and ECM remodeling in paracoccidioidomycosis.
Main Methods:
- BALB/c athymic (nu/nu) and euthymic (nu/+) mice were infected intraperitoneally with a virulent isolate of Paracoccidioides brasiliensis.
- Histologic examination of organ specimens was performed at 1, 4, and 7 weeks post-infection using various staining techniques.
- Analysis focused on collagen types (I and III), proteoglycans, reticular fibers, and the overall lesion architecture.
Main Results:
- Early lesions (1 week) in both groups showed predominance of collagen III over I, carboxylated proteoglycans, and tendency to encapsulation.
- Lesions in euthymic (nu/+) mice evolved towards involution or encapsulation with increased collagen I and sulfated proteoglycans from 4 weeks onward.
- Athymic (nu/nu) mice consistently displayed active lesions rich in reticular fibers and carboxylated proteoglycans, with minimal encapsulation, indicating a sustained-expansive type of lesion architecture.
Conclusions:
- The absence of T-cells in athymic mice leads to a sustained-expansive lesion type characterized by active fibrosis and minimal encapsulation during P. brasiliensis infection.
- Euthymic mice, with intact T-cell immunity, develop lesions that tend to involute or become encapsulated, suggesting immune control over fungal spread and tissue remodeling.
- The fundamental difference in lesion development between nude and normal mice lies in the overall architectural organization rather than isolated component differences, highlighting the critical role of T-cell immunity in modulating fibrosis and disease progression in paracoccidioidomycosis.