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

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

Author Munoz, Julian E. Google Scholar
Luft, Vinicius D. Google Scholar
Amorim, Juliana Google Scholar
Magalhes, Adriana Google Scholar
Thomaz, Luciana Google Scholar
Nosanchuk, Joshua D. Google Scholar
Travassos, Luiz R. Autor UNIFESP Google Scholar
Taborda, Carlos Pelleschi Autor UNIFESP Google Scholar
Institution Universidade de São Paulo (USP)
Montefiore Med Ctr
Albert Einstein Coll Med
Universidade Federal de São Paulo (UNIFESP)
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-gamma, IL-1 beta 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.
Keywords P. brasiliensis
Anergy
Chemotherapy
P10 immunization
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2007/58750-4
FAPESP: 2011/17267-4
FAPESP: 2010/51423-0
Date 2014-10-01
Published in Mycopathologia. Dordrecht: Springer, v. 178, n. 3-4, p. 177-188, 2014.
ISSN 0301-486X (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 177-188
Origin http://dx.doi.org/10.1007/s11046-014-9801-1
Access rights Closed access
Type Article
Web of Science ID WOS:000341865800003
URI http://repositorio.unifesp.br/handle/11600/38272

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