Immunomodulation of dendritic cells and cellular adaptive response promoted by extracellular vesicles obtained from P. brasiliensis yeasts extracted from chronic granulomatous lesions of C57BL/6 WT mice

• Grant number: 22/10654-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2022
• End date: August 31, 2023
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Flávio Vieira Loures
• Grantee: Monique Gama de Santana
• 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 important immunological structures in host defense against the dimorphic fungal Paracoccidioides brasiliensis, the main causative agent of Paracoccidioidomycosis (PCM), a chronic systemic mycosis endemic in several Latin America countries. The interaction of P. brasiliensis with the host tissue initially triggers a congestive-exsudative inflammatory reaction, with a predominance of influx of neutrophils. Progressively, these cells are replaced by macrophages, arranged in nodules and multinucleated giant cells. Disease development and granuloma formation depend on factors associated with the host's immune response and pathogen's characteristics, especially virulence factors. Extracellular vesicles (EVs) are lipid bilayer structures that transport molecules between the intracellular and extracellular environments. In the case of P. brasiliensis, some of the components exported by EVs are virulence factors and immunomodulatory compounds. Although some of the components of P. brasiliensis extracellular vesicles are known, the role of EVs in immunological modulation is still unknown, especially in cellular immunity, which is the main defense mechanism in PCM. Thus, the objective of this research is to analyze the immunomodulation of dendritic cells and the cellular adaptive response in vitro promoted by EVs obtained from P. brasiliensis yeasts extracted from granulomatous lung lesions of infected C57BL/6 WT mice, seeking to understand the immune response modulated by these fungal vesicles. In similar assays performed with macrophages, it was possible to observe that EVs from P. brasiliensis promote a pro-inflammatory response in macrophages.(AU)