Monoclonal antibodies to heat shock protein 60 induce a protective immune response against experimental Paracoccidioides lutzii

Autor(es)

Thomaz, Luciana ^[1] ; Nosanchuk, Joshua D. ^{[2, 3]} ; Rossi, Diego C. P. ^[1] ; Travassos, Luiz R. ^[4] ; Taborda, Carlos P. ^[5]

Afiliação do(s) autor(es)

^[1] Inst Biomed Sci, Dept Microbiol, BR-05508900 Sao Paulo - Brazil

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

^[3] 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, IMTSP LIM53, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Microbes and Infection; v. 16, n. 9, p. 788-795, SEP 2014.
• Citações Web of Science: 6

Resumo

Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin America. PCM is primarily caused by Paracoccidioides brasiliensis and less frequently by the recently described, closely related species Paracoccidioides lutzii. Current treatment requires protracted administration of systemic antibiotics and relapses may frequently occur despite months of initial therapy. Hence, there is a need for innovative approaches to treatment. In the present study we analyzed the impact of two monoclonal antibodies (mAbs) generated against Heat Shock 60 (Hsp60) from Histoplasma capsulatum on the interactions of P. lutzii with macrophages and on the experimental P. lutzii infection. We demonstrated that the Hsp60-binding mAbs labeled P. lutzii yeast cells and enhanced their phagocytosis by macrophage cells. Treatment of mice with the mAbs to Hsp60 before infection reduced the pulmonary fungal burden as compared to mice treated with irrelevant mAb. Hence, mAbs raised to H. capsulatum Hsp60 are protective against P. lutzii, including mAb 7B6 which was non-protective against H. capsulatum, suggesting differences in their capacity to bind to these fungi and to be recognized by macrophages. These findings indicate that mAbs raised to one dimorphic fungus may be therapeutic against additional dimorphic fungi, but also suggests that biological differences in diseases may influence whether a mAb is beneficial or harmful. (C) 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 07/53175-1 - Eficacia e funcao biologica de anticorpos monoclonais gerados contra antigenos de parede e exoantigenos de paracoccidoides brasiliensis na infeccao experimental
• Beneficiário: Luciana Thomaz
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• 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: 13/18655-3 - Paracoccidioides lutzii: desenvolvimento de vacina terapêutica a partir de antígenos específicos para serem utilizados em vacina combinada com o peptídeo P10 de P. brasiliensis
• Beneficiário: Carlos Pelleschi Taborda
• Modalidade de apoio: Auxílio à Pesquisa - Regular