Evaluation of the immunomodulatory potential of extracellular vesicles produced by Aspergillus fumigatus

• Grant number: 19/22454-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2020
• Effective date (End): June 21, 2021
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Fausto Bruno dos Reis Almeida
• Grantee: Mateus Silveira Freitas
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Aspergillus fumigatus is the causative agent of Invasive Aspergillosis, a disease that presents a high mortality rate, and mainly affects immunocompromised individuals. The fungus has a global distribution and a large production of conidia, causing the human respiratory tract to be continuously exposed. Normally the destruction of conidia, and control of infection, is carried out by innate imune cells. These are able to identify the fungus and its products, and respond appropriately. In this sense, we have that the Extracellular Vesicles (VEs) produced by the fungus could play an important role in the generation of immune response. In fact, the interaction of vesicles of other fungi with innate imune cells has already been described, demonstrating the immunomodulatory potential of these vesicles. Unpublished data from our group demonstrate that A. fumigatus is capable of producing such vesicles, but its importance in the host innate immune response remains undefined. In this way we propose to investigate the immunomodulatory properties of A. fumigatus VEs in the following aspects: (1) to evaluate, in vitro, the production of inflammatory mediators and cellular activity of macrophages, neutrophils and NK cells stimulated with VEs of A. Fumigatus; (2) to verify the importance of TLR-2, TLR-4 and Dectin-1 in the recognition of VEs of A. Fumigatus; (3) to evaluate the formation of NETs in neutrophils stimulated with VEs of A. Fumigatus; (4) to evaluate cytokine profile, histological pattern and cell population in the spleen and lung of mice stimulated with VEs of A. fumigatus. The fulfillment of these goals will allow to investigate the direct association between immunomodulatory activities of A. fumigatus VEs and fungal pathogenicity. Our expectation is that A. fumigatus VEs play an important role in the immunomodulation of host cells. (AU)