Authors: Luiz R. Travassos and Carlos P. Taborda

Luiz R. Travassos

Corresponding author: travassos@unifesp.br
Cell Biology Division, Department of Microbiology; Immunology and Parasitology; Federal University of São Paulo; São Paulo, Brazil

Carlos P. Taborda

Institute of Biomedical Sciences; Department of Microbiology and Laboratory of Medical Mycology IMT/SP- LIM53; University of São Paulo; São Paulo, Brazil

Abstract:
Paracoccidioidomycosis is a granulomatous pulmonary infection that is generally controlled by chemotherapy. The efficacy of treatment, however, is limited by the status of the host immune response. The inhibition of a Th-2 immunity or the stimulation of Th-1 cytokines generally increases the efficacy of antifungal drugs.¹ This has been achieved by immunization with an internal peptide of the major diagnostic antigen gp43 of Paracoccidioides brasiliensis. Peptide 10 (QTLIAIHTLAIRYAN) elicits an IFN-γ rich Th-1 immune response that protects against experimental intratracheal infection by this fungus. The combination of chemotherapy with P10 immunization showed additive protective effect even after 30 d of infection or in anergic mice, rendering in general, increased production of IL-12 and IFN-γ and reduction of IL-4 and IL-10. Immunotherapy with P10 even in the absence of simultaneous chemotherapy has been effective using various protocols, adjuvants, nanoparticles, P10-primed dendritic cells, and especially a combination of plasmids encoding the P10 minigene and IL-12. Gene therapy, in a long-term infection protocol succeeded in the virtual elimination of the fungus, preserving the lung structure, free from immunopathological side effects.

Received: June 15, 2012; Accepted: June 27, 2012; Published Online: August 16, 2012

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