Importance of proteases of Paracoccidioides Brasiliensis in host immune response

Abstract

Paracoccidioidomycosis (PCM) is the most prevalent systemic fungal infection in Brazil, its etiological agent is Paracoccidioides brasiliensis. The relationship between the fungus and the host is very complex and it is believed that, throughout evolution, the fungus has developed important mechanisms to manipulate the signaling pathways of the host cell, as well as the immune response in order to ensure their survival and establishment of infection.Some research groups have shown that the role of proteases in fungi is related to the ability of these microorganisms to destroy the host tissue, causing infections in skin, airway epithelium and other organs, making these molecules important virulence factors. In addition, fungi can express proteases that modulate the inflammatory response, by degrading important proteins for host immune response, such as cytokines and complement compounds, and by activating protease-activated receptors (PARs). Recently, our group demonstrated that proteases of P. brasiliensis yeasts cleave pro-inflammatory cytokines secreted by human lung epithelial cells.Thus, the project objectives are: i) characterization of proteases expressed in P.brasiliensis related to the degradation of the host cytokines ii) in the presence of P.brasiliensis, analyze the importance of PARs in epithelial cells for the secretion of cytokines, iii) identify the signaling pathways involved in the expression of PARs and other receptors (TLRs and Dectina-1) and iv) to analyze the importance of TLRs and Dectin-1 in the expression of PARs in A549 cells infected with P.brasiliensis. (AU)