Banca de QUALIFICAÇÃO: Amanda Pereira Rocha

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : Amanda Pereira Rocha
DATE: 15/02/2023
TIME: 14:00
LOCAL: Videoconferência
TITLE:

"The role of melanin and laccase 1 from Cryptococcus neoformans in inflammation and cell death of human macrophages."

KEY WORDS:

Criptococcosis, Cryptococcus neoformans, melanin, laccase 1, macrophages, infection, immunity, inflammation, cell death

PAGES: 72
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Cryptococcosis is an infectious disease caused by fungi from the genus Cryptococcus, the infection with C. neoformans being the most common and globally disseminated. It is estimated that 152 thousand new cases of cryptococcosis appear annually, which 73% of these cases lead to death. C. neoformans is able to produce melanin and now it is known that it acts as a virulence factor, facilitating infection. Melanin production is possible due to the presence of the enzyme laccase 1(LAC1) in the fungi. However, the role of the melanin and laccase 1 in the inflammation and death of the host cells still remain unclear. Therefore, in this work we investigate whether the presence of melanin and laccase 1 could interfere in inflammatory mediators produced by human macrophages and, consequently, in their death. We could notice that the presence of melanin as the lack of LAC1 provoked less phagocytosis by macrophages of C. neoformans but not change the number of yeast per cell. Moreover, C. neoformans infection caused more cell death, and melanin and LAC1 absence induce even more death after 24 hours. Investigating which type of death is trigged by etiologic agent, we discovered that in early infection (5 h.p.i) is induced apoptosis, whereas in late infection, apoptosis is greatly reduced and lytic death is the predominant type of death. The presence of melanin and the lack of LAC1 caused more lytic death. Since C. neoformans infection and its melanin provoked more death, we evaluated wether this death could be trigged by inflammasomes activation and despite we barely saw activation until 2 h.p.i, in early infection (5 h.p.i) we could notice there was cleavage and activation of caspase 1 (CASP1) and gasdermin D (GSDMD), which was more pronounced in late infection (24 h.p.i). However, it is visualized a greater caspase 8 activation in early infection when LAC1 is absent, compared to CASP1, while in late infection showed a massive activation of CASP1. This could explain the apoptosis increased at 5 h.p.i and the prevalence of lytic death in human macrophages at 24 h.p.i interacted with the yeast. Therefore, we conclude that C. neoformans is able to induce cell death in human macrophages during infection, which is trigged by inflammasome activation and its virulence factors could change this process.

BANKING MEMBERS:
Presidente - 2862542 - KELLY GRACE MAGALHAES
Externo à Instituição - PEDRO HENRIQUE MIRANDA BURGEL - IESB
Externo à Instituição - RAFAEL CORREA
Externa à Instituição - SUSANA FRASES CARVAJAL - UFRJ