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

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

Author Thomaz, Luciana Google Scholar
Nosanchuk, Joshua D. Google Scholar
Rossi, Diego C. P. Google Scholar
Travassos, Luiz R. Autor UNIFESP Google Scholar
Taborda, Carlos Pelleschi Autor UNIFESP Google Scholar
Institution Inst Biomed Sci
Albert Einstein Coll Med
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract 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.
Keywords Paracoccidioides lutzii
Monoclonal antibody
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 2007/53175-1
FAPESP: 2011/17267-4
FAPESP: 2013/18655-3
Date 2014-09-01
Published in Microbes and Infection. Amsterdam: Elsevier B.V., v. 16, n. 9, p. 788-795, 2014.
ISSN 1286-4579 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 788-795
Access rights Closed access
Type Article
Web of Science ID WOS:000347867100011

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