Identification, characterization and importance of circulating extracellular vesicles in the progression of fungal infection in patients with candidiasis, cryptococcosis and paracoccidioidomycosis

Author(s)

Caroline Patini de Rezende

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2024-01-29

Examining board members

Fausto Bruno dos Reis Almeida; Lysangela Ronalte Alves

• Advisor: Fausto Bruno dos Reis Almeida

Abstract

In recent years, fungal diseases have caused nearly 2 million deaths annually. It is estimated that there are around 1.5 million fungal species, of which the main pathogenic fungi responsible for causing serious diseases are Candida spp., Cryptococcus spp., Aspergillus spp., and Paracoccidioides spp. The increase in the incidence and prevalence of invasive mycoses in recent years shows the need to develop new therapeutic alternatives. Extracellular vesicles (EVs) have become important biomarkers, promoting the interaction of fungal cells with other organisms and playing an important role in the pathogen-host relationship. Given the enormous complexity of fungal EVs and the lack of clinical studies demonstrating their role in the course of infection in vivo, the objective of this study was to identify and understand the role of circulating EVs in clinical samples from patients affected by fungal infections. The results demonstrate the presence of EVs in the serum and urine of patients with infections caused by C. albicans, C. neoformans, and P. brasiliensis. Among the main secondary metabolites found, the presence of lipids stands out as important molecules for the physiological functions of EVs, with a predominance of the chemical classes of steroids, sphingolipids, and fatty acids. These metabolites present in EVs may be crucial in modulating the host\'s immune response, and given the above, the immunobiological activity of the obtained EVs was evaluated in vitro. The results suggest a polarization of a pro-inflammatory profile with the production of cytokines such as TNF-α, IFN-γ, and IL-6, as well as high expression of the iNOS, a marker of M1 response. Therefore, it is possible to suggest that circulating EVs in patients affected by fungal infections are involved in the pathophysiology of the disease and promote a better understanding of the role of EVs in the course of fungal infection in patients and in an in vitro model, demonstrating the potential use of EVs in new therapeutic strategies for treating systemic mycoses. (AU)

• FAPESP's process: 20/03215-1 - Identification and characterization of fungal extracellular vesicles in patients with Candidiasis, Cryptococcosis and Paracoccidioidomycosis
• Grantee: Caroline Patini de Rezende
• Support Opportunities: Scholarships in Brazil - Doctorate