Transcriptional and proteomic profile of Paracoccidiodes brasiliensis yeasts present in chronic granulomatous lesions of C57BL/6 WT mice

• Grant number: 19/17324-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2019
• End date: August 31, 2021
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Flávio Vieira Loures
• Grantee: Bruno Montanari Borges
• Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
• Associated research grant: 18/14762-3 - Immunosuppression in paracoccidioidomycosis: the regulatory role of myeloid-derived suppressor cells (MDSCs) on host immunity, tissue pathology and genetic adaptation of fungal cells, AP.JP2

Abstract

Granulomas are immunological structures important in the host defense against the thermally dimorphic fungus Paracoccidioides brasiliensis, the main agent causative of Paracoccidioidomycosis (PCM), a systemic chronic mycosis endemic several Latin America countries. The interaction of P. brasiliensis with host tissue initially triggers a congestive-exudative inflammatory reaction with a predominant influx of neutrophils. Progressively, these cells are replaced by macrophages, which are arranged in nodules and multinucleated giant cells. The development of the disease as well as the granuloma formation depends on factors associate with the host immune response and characteristics of the pathogens, especially the virulence factors. The aim of this project is study a transcriptional (RNA seq) and proteomic profile of P. brasiliensis removed from lung granulomatous lesions of infected mice and compared these data to those obtained from the initial inoculum. This approach aims to establish changes in the expression of proteins under stress conditions determined by the constant activity of the immune system inside the granuloma. Thus, our goal is to characterize genes involved with the adaptive response of P. brasiliensis during the establishment of the chronic phase of pulmonary infection to understand how the fungus adapts to the host. Future studies using methodologies to silence or delete specific coding genes to obtain P. brasiliensis mutant strains, as well as in vivo functional studies would reveal key molecules that could be used as targets for developing new therapeutic strategies for PCM. Transcriptome profiling of fungi infecting host tissues or in host-like conditions has shown that stress adaptation is a frequent feature which may reveal genes crucial for fungal virulence. (AU)