Título:	Avaliação do papel de opsoninas e vias de internalização de Cryptococcus neoformans na expressão de genes envolvidos na interação do fungo com macrófagos
Autor(es):	Pinho, Lorena de Oliveira
Orientador(es):	Nicola, Patrícia Albuquerque de Andrade
Coorientador(es):	Paes, Hugo Costa
Assunto:	Criptococose Fagocitose Fungos Macrófagos
Data de publicação:	15-Mai-2025
Data de defesa:	25-Nov-2024
Referência:	PINHO, Lorena de Oliveira. Avaliação do papel de opsoninas e vias de internalização de Cryptococcus neoformans na expressão de genes envolvidos na interação do fungo com macrófagos. 2024. 59 f., il. Dissertação (Mestrado em Medicina Tropical) — Universidade de Brasília, Brasília, 2024.
Abstract:	Cryptococcosis is an opportunistic disease caused by the encapsulated fungus Cryptococcus neoformans, which mainly affects immunocompromised individuals. The main feature of C. neoformans is its polysaccharide capsule, a key virulence factor that masks pathogen-associated molecular patterns on the fungal cell wall. The capsule hampers efficient recognition by the immune system, reducing phagocytosis and other microbicidal responses. Under in vitro conditions, the phagocytosis of C. neoformans is extremely low in the absence of opsonins, such as antibodies or complement system molecules. Although macrophages play a crucial role in the immune response to the fungus, they can act as intracellular hosts, allowing pathogen replication. This study aimed to investigate the gene expression of murine macrophages in response to the internalization of Cryptococcus neoformans opsonized with complement or anti-GXM monoclonal antibodies, to better understand the role of these opsonins in the immune response to cryptococcosis. Pathways of internalization mediated by macrophage Fc receptors and complement receptors were analyzed, evaluating the effect of blocking these pathways with specific antibodies in phagocytosis assays. It was observed that the blockage in the conditions used only partially reduced fungal internalization. Subsequently, interaction assays were conducted with macrophages exposed to C. neoformans cells opsonized with guinea pig serum or with the antiglucuronoxylomannan monoclonal antibody, a major polysaccharide present in the fungus's capsule. After two hours of infection, the macrophages were collected for RNA extraction and gene expression analysis by RT-qPCR, focusing on the activation of genes related to the immune response to the fungus. The results did not show significant changes in the expression of 12 genes associated with the immune response of macrophages, both compared to the non-opsonized control and between the samples opsonized with serum or antibody. These findings suggest that differences in the immune response mediated by these two opsonins may be more subtle, indicating the need to investigate other genes and interaction times to better understand the possible differences mediated by different opsonins in the fungusmacrophage interaction.
Unidade Acadêmica:	Faculdade de Medicina (FM)
Informações adicionais:	Dissertação (mestrado) — Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Medicina Tropical, 2024.
Programa de pós-graduação:	Programa de Pós-Graduação em Medicina Tropical
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