Detrimental Effect of Fungal 60-kDa Heat Shock Protein on Experimental Paracoccidioides brasiliensis Infection

Author(s)

Fernandes, Fabr-Cio Freitas ; de Oliveira, Leandro Licursi ; Landgraf, Taise Natali ; Peron, Gabriela ; Costa, Marcelo Vieira ; Coelho-Castelo, Arlete A. M. ; Bonato, Vania L. D. ; Roque-Barreira, Maria-Cristina ; Panunto-Castelo, Ademilson

• Document type: Journal article
• Source: PLoS One; v. 11, n. 9 SEP 6 2016.
• Web of Science Citations: 3

Abstract

The genus Paracoccidioides comprises species of dimorphic fungi that cause paracocci-dioidomycosis (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-alpha, IL-12, IFN-gamma, IL-4, IL-10, and TGF-beta 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. (AU)

• FAPESP's process: 09/03235-3 - Characterization, cloning and expression of a Paracoccidioides brasiliensis protein with suppressive activity of the immune response.
• Grantee: Fabrício Freitas Fernandes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/12278-3 - Screening of Paracoccidioides brasiliensis antigens with potential immunotherapeutic application in paracoccidioidomicose
• Grantee: Ademilson Panunto-Castelo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/08552-0 - Identification of antigens from Paracoccidioides brasiliensis with immunotherapeutic potential for the treatment of paracoccidioidomycosis.
• Grantee: Taise Natali Landgraf
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 09/14777-1 - Gene cloning, expression and characterization of a protein from Paracoccidioides brasiliensis with immunosuppressive activity in experimental paracoccidioidomycosis.
• Grantee: Ademilson Panunto-Castelo
• Support Opportunities: Regular Research Grants