Estudo do impacto das vesículas extracelulares liberadas por Paracoccidioides lutzii, após cultivo em condições de privação e suficiência de ferro, na fagocitose por macrófagos in vitro
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Data
2024-11-29
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Universidade Federal de Goiás
Resumo
Introduction: Extracellular vesicles (EVs) are membrane-enclosed structures released by cells into
the extracellular space and play fundamental roles in biological processes and in the regulation of
the immune response. In the context of the fungus Paracoccidioides lutzii, the causative agent of
paracoccidioidomycosis, a systemic granulomatous mycosis prevalent in Brazil, it was observed that
the production and release of EVs are influenced by environmental conditions, such as iron
restriction. Iron is essential for the metabolic functions of the fungus, and deprivation of this mineral
appears to significantly impact both the production and content of EVs. These vesicles are crucial
for the interaction of P. lutzii with the host, including immune cells such as macrophages, where they
can modulate the immune response and the pathogenesis of the infection. Objectives: The aim of
this study was to analyze the effect of EVs released by P. lutzii, after cultivation of the fungus under
iron deprivation and sufficiency conditions, on the phagocytosis of the fungus by macrophages in
vitro. Methodology: To investigate this hypothesis, P. lutzii were cultured weekly in Brain Heart
Infusion agar and in solid Modified Minimal Medium (MVM), under iron deprivation (supplemented
with bathophenanthroline disulfonic acid, BPS) and under iron sufficiency conditions (supplemented
with Fe (NH4)2(SO4)2). Then, phagocytosis assays were conducted, where the ability of
macrophages to inactivate the fungus (CMIF) and the intracellular proliferation index (IPR) were
evaluated. Results: Stimulation with IFNγ increases the inactivation of P. lutzii in macrophages after
6 hours, evidencing its role in microbicidal activation. However, after 24 hours, VEsFe and VEsBPS
induced an increase in intracellular fungal proliferation, suggesting a negative immunomodulatory
effect. After changing the medium, only IFNγ maintained the significant reduction in fungal growth,
while VEs did not alter the interaction with macrophages, indicating a limited effect in modulating
the immune response. Conclusion: The results indicate that IFNγ has a fundamental role in the
microbicidal activity of macrophages, significantly reducing the proliferation of P. lutzii. In contrast,
extracellular vesicles (VEsFe and VEsBPS) present a negative immunomodulatory effect, favoringthe increase in fungal growth at 24 hours, which suggests that they may interfere with the ability of
macrophages to control the infection. After changing the culture medium, only IFNγ continued to
inhibit fungal growth. These findings highlight the therapeutic potential of IFNγ and the need for
further studies on the effects of extracellular vesicles.
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Palavras-chave
Paracoccidioides lutzii, Vesículas extracelulares, Suficiência de ferro, Privação de ferro, Macrófagos, Extracellular vesicles, Iron sufficiency, Iron deprivation, Macrophages
Citação
ALVES, Samilly Cesário. Estudo do impacto das vesículas
extracelulares liberadas por Paracoccidioides lutzii, após cultivo em
condições de privação e suficiência de ferro, na fagocitose por
macrófagos in vitro. 2024. 35 f. Trabalho de Conclusão de Curso
(Bacharelado em Biomedicina) – Instituto de Ciências
Biológicas, Universidade Federal de Goiás, Goiânia, 2024