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Immunization with P10 Peptide Increases Specific Immunity and Protects Immunosuppressed BALB/c Mice Infected with Virulent Yeasts of Paracoccidioides brasiliensis

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Abstract

Paracoccidioidomycosis is a systemic granulomatous disease caused by Paracoccidioides spp. A peptide from the major diagnostic antigen gp43, named P10, induces a T-CD4+ helper-1 immune response in mice and protects against intratracheal challenge with virulent P. brasiliensis. Previously, we evaluated the efficacy of the P10 peptide alone or combined with antifungal drugs in mice immunosuppressed and infected with virulent isolate of P. brasiliensis. In the present work, our data suggest that P10 immunization leads to an effective cellular immune response associated with an enhanced T cell proliferative response. P10-stimulated splenocytes increased nitric oxide (NO) production and induced high levels of IFN-γ, IL-1β and IL-12. Furthermore, significantly increased concentrations of pro-inflammatory cytokines were also observed in lung homogenates of immunized mice. P10 immunization was followed by minimal fibrosis in response to infection. Combined with antifungal drugs, P10 immunization most significantly improved survival of anergic infected mice. Administration of either itraconazole or sulfamethoxazole/trimethoprim together with P10 immunization resulted in 100 % survival up to 200 days post-infection, whereas untreated mice died within 80 days. Hence, our data show that P10 immunization promotes a strong specific immune response even in immunocompromised hosts and thus P10 treatment represents a powerful adjuvant therapy to chemotherapy.

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Acknowledgments

This work was supported by grants 2007/58750-4, 2011/17267-4 and 2010/51423-0 from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). We acknowledge the valuable technical assistance of the Laboratory the Immunohistochemistry of Department of Anatomy, School of Veterinary Medicine and Animal Science, University of São Paulo, and of Carlos da Silva and the animal facility of Department of Microbiology, University of São Paulo.

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Authors and Affiliations

  1. Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1374, São Paulo, SP, 05008-900, Brazil

    Julián E. Muñoz, Vinicius D. Luft, Juliana Amorim, Adriana Magalhães, Luciana Thomaz & Carlos P. Taborda

  2. Departments of Medicine, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA

    Joshua D. Nosanchuk

  3. Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo, SP, Brazil

    Luiz R. Travassos

  4. Laboratory of Medical Mycology-LIM53/IMTSP, University of São Paulo, São Paulo, SP, Brazil

    Carlos P. Taborda

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  1. Julián E. Muñoz
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  2. Vinicius D. Luft
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  8. Carlos P. Taborda
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Correspondence to Carlos P. Taborda.

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Muñoz, J.E., Luft, V.D., Amorim, J. et al. Immunization with P10 Peptide Increases Specific Immunity and Protects Immunosuppressed BALB/c Mice Infected with Virulent Yeasts of Paracoccidioides brasiliensis . Mycopathologia 178, 177–188 (2014). https://doi.org/10.1007/s11046-014-9801-1

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  • DOI: https://doi.org/10.1007/s11046-014-9801-1

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