14th ICID - Poster Abstracts - International Society for Infectious ...

When citing these abstracts please use the following reference:
Author(s) of abstract. Title of abstract [abstract]. Int J Infect Dis 2010;14S1: Abstract number.
Please note that the official publication of the International Journal of Infectious Diseases 2010, Volume 14, Supplement 1
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Final Abstract Number: 30.014
Session: Mycology, Fungal Infections and Antifungal Drugs
Date: Wednesday, March 10, 2010
Time: 12:30-13:30
Room: Poster & Exhibition Area/Ground Level
Type: Poster Presentation
Granulomatous lesions in experimental Paracoccidioides brasiliensis infection
E. Burger 1 , R. F. S. Molina 2 , J. V. Alves 2 , C. R. P. Pizzo 2 , A. S. Nishikaku 2
1 Universidade Federal do Espirito Santo; Universidade de Sao Paulo, Sao Mateus e Sao Paulo,
Espirito Santo e Sao Paulo, Brazil, 2 Universidade de São Paulo, Sao Paulo, Sao Paulo, Brazil
Background: Paracoccidioidomycosis (PCM) is a systemic mycosis, caused by the fungus
Paracoccidioides brasiliensis (Pb), that affects healthy individuals living in rural areas in Latin
America. There are many clinical forms of the disease; severe forms are characterized by the
presence of numerous disseminated granulomatous lesions, anergy in cellular immunity and high
levels of specific antibodies, in contrast, mild forms have few localized granulomatous lesions,
preserved cellular immunity and low levels of specific antibodies. Granuloma formation can be
interpreted as a host defense mechanism to destroy or contain Pb and avoid its dissemination.
Methods: We infected susceptible (S) and resistant (R) mice with Pb to study the granulomas.
We analysed the architecture of the granulomas and associated with presence of morphologically
preserved or destroyed Pb, deposition of some extracellular matrix (ECM) components (collagen
fibers types I, II, IV, osteopontin, laminin, biglycan, decorin), presence of relevant cytokines to
granuloma formation (-IFN, TGF-, TNF-) and of matrix metalloproteinases (MMP).
Results: We detected all the above mentioned elements in the lesions. The thick fibers of
collagen type I, (R>S) may be associated with Pb infection containment; the thin reticular fibers of
collagen type III may promote the microenvironment for Pb-cell-ECM interactions; the marker of
newly formed vessels collagen type IV may promote Pb dissemination and favor the influx of
inflammatory cells and the proteoglycans biglycan and decorin, (R>S) may promote fungal
containment. The cytokines TNF- and -IFN, this later more observed in R mice may promote
macrophage activation, enhancing Pb killing by these cells and the control fungal dissemination;
TGF-, (S>R) may promote deactivation and inhibition of Pb killing by macrophages, favoring
fungal dissemination and osteopontin may favor infection at its onset (S>R) and promote
protection later (R>S). MMP-9 was detected in both S and R mice with active infection, eventually
being involved in fungal dissemination.
Conclusion: The fate of PCM infection locally depends of the combined effects of ECM
components, which can be limiting or permissive to Pb dissemination, and those of cytokines,
which can either activate or inactivate phagocytic cells, leading to Pb lysis or survival.