title: Monoclonal antibodies to heat shock protein 60 induce a protective immune response against experimental Paracoccidioides lutzii.
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.
authors.affiliation: Institute of Biomedical Sciences, Department of Microbiology, Brazil. Electronic address: lucithomaz@usp.br.
authors.forename: Luciana
authors.initials: L
authors.lastname: Thomaz
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
authors.affiliation: Institute of Biomedical Sciences, Department of Microbiology, Brazil.
authors.forename: Diego C P
authors.initials: DC
authors.lastname: Rossi
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Travassos
authors.affiliation: Institute of Biomedical Sciences, Department of Microbiology, Brazil; Laboratory of Medical Mycology IMTSP- LIM53 University of São Paulo, São Paulo, Brazil.
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Taborda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000946:Antigens, Fungal / Q000276:immunology; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D006658:Histoplasma / Q000276:immunology; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010228:Paracoccidioides; D010229:Paracoccidioidomycosis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000382:microbiology
chemical_list: D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D018834:Chaperonin 60; D016207:Cytokines
keywords: Hsp60; Monoclonal antibody; Paracoccidioides lutzii