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Cyclosporin A Treatment and Decreased Fungal Load/Antigenemia in Experimental Murine Paracoccidioidomycosis

Mycopathologia volume 171, pages 161–169 (2011)Cite this article

Abstract

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb). The cyclosporin A (CsA) is an immunosuppressant drug that inhibits calcineurin and has been described as a potential antifungal drug. The present study investigated the effect of CsA on the immune response, fungal load/antigenemia in experimental murine PCM. It was used four groups of BALB/c mice: (a) infected with 1 × 105 Pb18 yeast cells (Pb), (b) infected and treated with CsA every other day 10 mg/kg of CsA (s.c.) during 30 days (Pb/CsA), (c) treated with CsA (CsA) and (d) no infected/treated (PBS). The immune response was evaluated by lymphocyte proliferation, DTH assays to exoAgs, ELISA for IgG anti-gp43 (specific immune responses) and cytokine serum levels (IFN-γ, TNF-α, IL-4 and IL-10). Fungal load was determined by lung colony-forming units (CFU) counts, lung and liver histopathology analysis and antigenemia determined by inhibition-ELISA. As expected, CsA was able to inhibit the specific cellular and humoral immune response (P < 0.05), with decrease in serum IFN-γ, TNF-α and IL-4 levels (P < 0.05). Cyclosporin A treatment also resulted in significantly decreased lung Pb CFU (P < 0.05) as well as a lower number of yeasts in the lung and liver (P < 0.05) by histopathology. In concordance, the decreased antigenemia was observed in Pb/CsA group (P < 0.05). In conclusion, even with immunosuppressive action, treatment with CsA results in decreased lung fungal load/antigenemia in experimental PCM in BALB/c mice. Further study is required to determine whether this represents less severe disease or protection by CsA.

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Acknowledgments

This work was supported by Secretaria de Estado da Ciencia, Tecnologia e Ensino Superior (SETI/PR), Fundação Araucária/PR, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). We thank Dr. Everson A. Nunes for his careful correction of the English language.

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Affiliations

  1. Department of Pathology Sciences, State University of Londrina, CCB, Universidade Estadual de Londrina, Campus Universitário, Londrina, PR, 86051-970, Brazil

    T. Y. C. Massuda, L. A. Nagashima, P. C. Leonello, M. S. Kaminami, M. S. Mantovani, E. J. Venancio & E. N. Itano

  2. Medical Mycology Research Center, Chiba University, Chiba, Japan

    A. Sano & J. Uno

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

    Z. P. Camargo

Authors
  1. T. Y. C. Massuda
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  2. L. A. Nagashima
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  3. P. C. Leonello
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  4. M. S. Kaminami
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  5. M. S. Mantovani
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  6. A. Sano
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  7. J. Uno
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  8. E. J. Venancio
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  9. Z. P. Camargo
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  10. E. N. Itano
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Correspondence to E. N. Itano.

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Massuda, T.Y.C., Nagashima, L.A., Leonello, P.C. et al. Cyclosporin A Treatment and Decreased Fungal Load/Antigenemia in Experimental Murine Paracoccidioidomycosis. Mycopathologia 171, 161–169 (2011). https://doi.org/10.1007/s11046-010-9359-5

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  • DOI: https://doi.org/10.1007/s11046-010-9359-5

Keywords

  • Immunosuppression
  • Paracoccidioides brasiliensis
  • Antifungal drug
  • Calcineurin
  • Cytokines
  • Lymphoproliferative response