Silencing and overexpression of paracoccin in Paracoccidioides Brasiliensis: effect on macrophage polarization

• Grant number: 18/21171-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2019
• Effective date (End): December 31, 2019
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Nayla de Souza Pitangui
• Grantee: Alany Cristina da Silva Nunes
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Species of the genus Paracoccidioides spp. are pathogenic, theriomorphic fungi and etiological agents of Paracoccidioidomycosis (PCM), the main mycosis of Latin America. The individual infected with Paracoccidioides spp. develops an answer against the fungus as a way of eliminating it from the organism. Resistance to infection by P. brasiliensis isassociated with the secretion of high levels of TNF-± and IFN-³. Many efforts have been developed to characterize fungal components important for their virulence, using gene silencing techniques in different pathogenic fungi. Our group identified the lectin paracoccin as a component of the yeasts of P. brasiliensis, which is the target of this project. This lectin binds to N-acetylglucosamine, contributes to the growth of the fungus and its adhesion to the extracellular matrix. In addition, it induces macrophages to produce TNF-± and high NO concentrations and interacts with TLR2 and TLR4. Silencing and gene overexpression of paracoccin showed that this chitinase is an important virulence factor in P. brasiliensis. Considering the relevance of the biological roles played by paracoccin, we propose to study the polarization of murine macrophages in vitro and in vivo after stimulation with the P. brasiliensis wt-PCN, ov-PCN and kd-PCN strains, and the fungal load on the lung of infected animals. The results obtained may contribute to the understanding of paracoccin participation in fungal biology and the course of experimental PCM.