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Immunohistochemical demonstration of TGF-beta and decorin in paracoccidioidal granulomas
1Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
Abstract:
Different patterns of granulomas have been observed in 6- to 8-week-old mice after ip inoculation with 5 x 10(6) yeast cells of Paracoccidioides brasiliensis. Transforming growth factor-beta (TGF-beta) is a cytokine that has been shown to participate in fibrosis and granuloma formation; its activities seem to be modulated by the small proteoglycan decorin. In the present study, TGF-beta and decorin expression in epiploon granulomas was assessed by immunohistochemistry in susceptible (B10.A) and resistant (A/J) mice after 15, 30, 120 and 150 days of P. brasiliensis ip infection. The epiploon was collected, fixed in Methacarn solution and embedded in paraffin, and 5-microm thick sections were used for immunohistochemical analysis employing the streptavidin-biotin-peroxidase technique. The former mouse strain developed fatal disease with many disseminated lesions increasing in size and number during the infection and the latter developed mild disease with the presence of encapsulated granulomas. In the epiploon, TGF-beta was present on macrophages, giant cells, lymphocytes and fibroblasts, and absent on neutrophils. It was also detected in areas of fibrosis and necrosis, as well as disperse in amorphous extracellular matrix, mostly in resistant mice. Decorin was present circumscribing macrophages and giant cells containing fungi, but absent on these cells. In both mouse strains, decorin was found at the periphery of the lesions, and markedly in milky spot granulomas. In resistant mice, positivity was found around fibrotic and necrotic areas of encapsulated and residual lesions containing lysed fungi. Decorin was found associated with thick fibers around encapsulated lesions. In susceptible mice, the size and number of lesions increased with the progression of the disease and were correlated with the weaker expression of decorin. We suggest an association of decorin with the fibrogenic process observed in paracoccidioidal granulomas.
Insights
This study reveals that decorin expression is linked to the fibrogenic process in Paracoccidioides brasiliensis granulomas, with weaker decorin correlating to more severe disease in mice.
Area of Science:
- Immunology
- Pathology
- Microbiology
Background:
- Granuloma formation is a key host response to fungal infections like Paracoccidioides brasiliensis.
- Transforming growth factor-beta (TGF-beta) is implicated in fibrosis and granuloma development.
- Decorin, a small proteoglycan, may modulate TGF-beta activity and influence tissue remodeling.
Purpose of the Study:
- To investigate the expression patterns of TGF-beta and decorin in the epiploon granulomas of susceptible and resistant mice infected with P. brasiliensis.
- To explore the potential association of decorin with the fibrogenic process in paracoccidioidal granulomas.
Main Methods:
- Immunohistochemistry was used to assess TGF-beta and decorin expression in mouse epiploon granulomas at various time points post-infection.
- Susceptible (B10.A) and resistant (A/J) mouse strains were infected with P. brasiliensis.
- Streptavidin-biotin-peroxidase technique was employed on paraffin-embedded tissue sections.
Main Results:
- TGF-beta was detected in macrophages, giant cells, lymphocytes, fibroblasts, and extracellular matrix, particularly in resistant mice.
- Decorin was found around fungal-containing cells and at lesion peripheries, associated with fibrotic areas and thick fibers in resistant mice.
- Susceptible mice showed increased lesion size and number correlated with weaker decorin expression.
Conclusions:
- Decorin expression is associated with the fibrogenic process in paracoccidioidal granulomas.
- Differential expression of decorin may contribute to varying disease outcomes in P. brasiliensis infection.
- Further research into decorin's role could offer insights into managing fungal granulomatous diseases.

