Paracoccidioides brasiliensis induces cytokine secretion in epithelial cells in a protease-activated receptor-dependent (PAR) manner

Author(s)

de Oliveira, Priscila ; Juliano, Maria Aparecida ; Tanaka, Aparecida Sadae ; Carmona, Adriana Karaoglanovic ; Batista dos Santos, Saara Maria ; Silva Campitelli de Barros, Bianca Carla ; Maza, Paloma Korehisa ; Puccia, Rosana ; Suzuki, Erika

• Document type: Journal article
• Source: MEDICAL MICROBIOLOGY AND IMMUNOLOGY; v. 206, n. 2, p. 149-156, APR 2017.
• Web of Science Citations: 2

Abstract

Paracoccidioides brasiliensis is one of the etiological agents of the human systemic mycosis paracoccidioidomycosis. Protease-activated receptors (PARs) are expressed in many cell types and comprise a family of G protein-coupled receptors (PAR-1, PAR-2, and PAR-4), which may be activated by proteases secreted by several pathogens. In the present study, we showed that the pathogenic fungus P. brasiliensis secretes components that promote interleukin (IL)-6 and IL-8 secretion by the lung epithelial cell line A549. Cytokine secretion was reduced by antagonistic peptides for PAR-1 and PAR-2, but not for PAR-4. P. brasiliensis proteases were isolated from fungal culture supernatants in a p-aminomethylbenzamidine-Sepharose column. The obtained fractions were tested for enzymatic activity against fluorescence resonance energy transfer (FRET) peptides derived from sequences that spanned the activation sites of human PARs. The eluted fraction, termed PbP, contained protease activities that were able to hydrolyze the FRET peptides. PbP also induced IL-6 and IL-8 secretion in A549 epithelial cells, which was reduced upon heat inactivation of PbP, incubation with antagonistic peptides for PAR-1 and PAR-2, and the protease inhibitors aprotinin, leupeptin, and E-64. Together, these results show for the first time that P. brasiliensis yeasts secrete proteases that activate PARs in lung epithelial cells, leading to cytokine secretion. (AU)

• FAPESP's process: 11/23096-8 - Importance of proteases of Paracoccidioides Brasiliensis in host immune response
• Grantee: Priscila de Oliveira Colombo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/22773-6 - Studies of the mechanisms of adhesion and cytokine modulation during interaction of epithelial cells and pathogenic fungi
• Grantee: Erika Suzuki de Toledo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/25652-6 - Study of the communication between receptors, and their signaling pathways, in fungus-induced cytokine secretion in epithelial cells
• Grantee: Erika Suzuki de Toledo
• Support Opportunities: Regular Research Grants