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

Autor(es)

Munoz, Julian E. ^[1] ; Luft, Vinicius D. ^[1] ; Amorim, Juliana ^[1] ; Magalhes, Adriana ^[1] ; Thomaz, Luciana ^[1] ; Nosanchuk, Joshua D. ^{[2, 3]} ; Travassos, Luiz R. ^[4] ; Taborda, Carlos P. ^{[1, 5]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Microbiol, Inst Biomed Sci, BR-05008900 Sao Paulo - Brazil

^[2] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 - USA

^[3] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 - USA

^[4] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Lab Med Mycol LIM53 IMTSP, BR-05008900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Mycopathologia; v. 178, n. 3-4, p. 177-188, OCT 2014.
• Citações Web of Science: 15

Resumo

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. (AU)

• Processo FAPESP: 11/17267-4 - Avaliação de uma vacina baseada no peptídeo-P10 e seu efeito terapêutico quando administrado em combinação com antifúngicos no modelo da fibrose experimental induzido com conídios de Paracoccidioides Brasiliensis
• Beneficiário: Carlos Pelleschi Taborda
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/58750-4 - Avaliação dos peptídeo sintético (P10): como adjuvante ao tratamento quimioterápico e sua resposta pulmonar em camundongos Balb/c anérgicos infectados com Paracoccidioides brasiliensis
• Beneficiário: Julián Esteban Muñoz Henao
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 10/51423-0 - Peptídeos bioativos e peptidases: atividades biológicas e imunobiológicas em doenças infecciosas e no câncer
• Beneficiário: Luiz Rodolpho Raja Gabaglia Travassos
• Modalidade de apoio: Auxílio à Pesquisa - Temático