Detrimental Effect of Fungal 60-kDa Heat Shock Protein on Experimental Paracoccidioides brasiliensis Infection.
The genus Paracoccidioides comprises species of dimorphic fungi that cause paracoccidioidomycosis (PCM), a systemic disease prevalent in Latin America. Here, we investigated whether administration of native 60-kDa heat shock protein of P. brasiliensis (nPbHsp60) or its recombinant counterpart (rPbHsp60) affected the course of experimental PCM. Mice were subcutaneously injected with nPbHsp60 or rPbHsp60 emulsified in complete's Freund Adjuvant (CFA) at three weeks after intravenous injection of P. brasiliensis yeasts. Infected control mice were injected with CFA or isotonic saline solution alone. Thirty days after the nPbHsp60 or rPbHsp60 administration, mice showed remarkably increased fungal load, tissue inflammation, and granulomas in the lungs, liver, and spleen compared with control mice. Further, rPbHsp60 treatment (i) decreased the known protective effect of CFA against PCM and (ii) increased the concentrations of IL-17, TNF-α, IL-12, IFN-γ, IL-4, IL-10, and TGF-β in the lungs. Together, our results indicated that PbHsp60 induced a harmful immune response, exacerbated inflammation, and promoted fungal dissemination. Therefore, we propose that PbHsp60 contributes to the fungal pathogenesis.
Department of Cellular and Molecular Biology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.
Fabrício Freitas
FF
Fernandes
Department of General Biology, Federal University of Viçosa, Viçosa, MG, Brazil.
Leandro Licursi de
LL
Oliveira
Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Taise Natali
TN
Landgraf
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
Gabriela
G
Peron
Department of Biology, Ribeirão Preto Faculty of Philosophy, Sciences and Letters, University of São Paulo, Ribeirão Preto, SP, Brazil.
Marcelo Vieira
MV
Costa
Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Arlete A M
AA
Coelho-Castelo
Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Vânia L D
VL
Bonato
Department of Cellular and Molecular Biology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.
Maria-Cristina
MC
Roque-Barreira
Department of Biology, Ribeirão Preto Faculty of Philosophy, Sciences and Letters, University of São Paulo, Ribeirão Preto, SP, Brazil.
Ademilson
A
Panunto-Castelo
D000818:Animals; D000946:Antigens, Fungal / Q000008:administration & dosage*; D018834:Chaperonin 60 / Q000008:administration & dosage*; D018450:Disease Progression; D005620:Freund's Adjuvant / Q000008:administration & dosage; D005656:Fungal Proteins / Q000008:administration & dosage*; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010228:Paracoccidioides / Q000254:growth & development / Q000472:pathogenicity*; D010229:Paracoccidioidomycosis / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D011994:Recombinant Proteins / Q000008:administration & dosage; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D000946:Antigens, Fungal; D018834:Chaperonin 60; D005656:Fungal Proteins; D007378:Interleukins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D005620:Freund's Adjuvant