Effect of fungal infections on the central nervous system: Candida spp. interactions with neurological and immunological cells

• Grant number: 22/06402-2
• Support Opportunities: Generation Project Research Grant
• Duration: September 01, 2023 - December 31, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Thais Fernanda de Campos Fraga da Silva
• Grantee: Thais Fernanda de Campos Fraga da Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Alessandro dos Santos Farias ; Eduardo Villablanca ; Fausto Bruno dos Reis Almeida ; Juliana Campos Junqueira ; Marimélia Aparecida Porcionatto ; Vânia Luiza Deperon Bonato
• Associated scholarship(s): 23/10692-9 - Effect of fungal infections on the central nervous system: Candida spp. interactions with neurological and immunological cells, BP.GR

Abstract

Fungi of the genus Candida are part of the human microbiota, but they are also responsible for invasive infections, which can affect the central nervous system (CNS). The fungal cell or derivatives, such as extracellular vesicles, can interact with resident cells and still activate immune responses, affecting homeostasis and inflammatory processes in the CNS. We hypothesized that after infections with Candida spp., the activation or death of resident cells, such as microglia, astrocytes, oligodendrocytes and neurons, associated to leukocytes influx to the CNS, triggered neuroinflammation. To test this hypothesis, we aim to evaluate the effect of medically important species of Candida in the neuroinflammation and also the mechanisms involved in this process. The study will focus on the virulence factors of Candida albicans, C. auris, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis and their interaction with neurological and immunological cells. Therefore, in this project we will use experimental models of invertebrate (Galleria mellonella larvae) and vertebrate (mice) animals, samples from patients with multiple sclerosis and in vitro models with cell lines and microplataforms (3D bioprinting) to mimicry CNS. This new line of research has the potential to establish collaborations with researchers from different institutions in Brazil and outside, and will directly favor the diversification of research at host institution. The results obtained in this project may help to establish new paradigms on the topic of invasive fungal infections that affect the CNS. (AU)