XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:74-1

Oral / Poster

74-1	Granuloma formation in the lungs of anergic mice immunized with peptide (P10) and submitted to chemotherapy in experimental paracoccidioidomycosis ਀
Authors:	Julian Esteban Muñoz Henao (USP - Universidade de São Paulo) ; Vinicius Dornelles Luft (USP - Universidade de São Paulo) ; Luiz Rodolpho Raja Gabaglia Travassos (UNIFESP - Universidade Federal de São Paulo) ; Carlos Pelleschi Taborda (USP - Universidade de São Paulo)

Abstract

Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by Paracoccidioides brasiliensis, a thermal dimorphic fungus. Endemic in Latin America and found mainly in Brazil, Colombia, Argentina and Venezuela. Mainly affecting rural workers. Inhalation of conidia is the probable route of infection. It has multiple manifestations, and two progressive forms (acute and chronic) are recognized. In most cases, PCM installs primarily in the lungs and then disseminates to other organs and systems. PCM treatment is currently based on sulfamethoxazole/trimethoprim, amphotericin B and azolic derivatives. The fungus secretes a glycoprotein of 43 kDa, with an internal peptide (QTLIAIHTLAIRYAN) calletd P10 containing a T-CD4+ epitope. Previously, we showed that P10 induced a protective immune response even in anergic mice. Presently we examined by immunohistochemistry the granuloma formation in these animals after vaccination with P10. We used monoclonal antibodies against macrophages (CD11b), neutrophils (Ly-6G) and T CD4+ lymphocytes (CD4+/L3T4). Anergy was induced by dexamethasone treatment for 20 days. Anergic BALB/c mice were then infected i.t. with 3x105 of Pb18.Thirty days after infection, mice were immunized with P10 associated or not with sulfamethoxazole/trimethoprim. Control animals (only infected) showed a great number of yeast cells with a cellular infiltrate without organization. Mice submitted to P10 immunization showed granuloma formation with migration of macrophages, neutrophils and T CD4+ lymphocytes. Animals immunized with P10 and submitted to anti-fungal drugs had the lungs virtually cleared of fungal cells with 100% survival after 200 days in contrast to the untreated anergic mice. The present study shows that P10 immunization promotes granuloma formation even in immunocompromised hosts.

Keyword: P10, sulfamethoxazole-trimethoprim, Anergy, P. brasiliensis, paracoccidioidomycosis

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