Banca de DEFESA: PAULA ROCHA DANTAS SILVA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : PAULA ROCHA DANTAS SILVA
DATE: 27/12/2023
TIME: 14:00
LOCAL: IGM Sala Virtual 5
TITLE:

Expression of autophagic pathway genes in Mycobacterium tuberculosis infection and effect of coinfection with human immunodeficiency virus (HIV)

KEY WORDS:

autophagy, tuberculosis, HIV, gene expression, LC3 expression.

PAGES: 110
BIG AREA: Ciências Biológicas
AREA: Imunologia
SUMMARY:

ABSTRACT
INTRODUCTION: Tuberculosis (TB) is an infection caused in humans mainly by Mycobacterium tuberculosis (Mtb) and constitutes a serious global public health problem. Mtb is an intracellular pathogen that has a tropism for humans and mainly causes pulmonary tuberculosis. Tuberculosis co-infection in people living with HIV (PLHIV) is of great concern at a global level, since TB is the infection that affects them most and the main cause of death due to intracellular pathogens in PLWH. Autophagy, in turn, is a physiological process responsible for the removal of non-functional cellular components and under conditions of nutrient deprivation, functional cellular components can be digested to generate energy for the cell. This mechanism involves the formation of a double-membrane vesicle called an autophagosome, which encompasses components of the cytoplasm, including macromolecules and organelles and, after fusion with the lysosome, digests the contents through the action of lysosomal enzymes. Autophagy has been associated with the intracellular elimination of pathogens such as Mtb and HIV. METHODS: The present study evaluated the expression of genes related to autophagy in volunteers infected with Mtb or HIV and co-infected by Mtb and HIV and the expression of LC3 in macrophages derived from THP-1 lineage monocytes infected with different mycobacteria to understand how autophagy can modulate and influence tuberculosis infection and HIV co-infection. RESULTS: From the evaluation of the gene expression profile related to autophagy, it was possible to observe that most of the autophagy pathway genes had a higher expression in the TB and TB-HIV groups. The ATG4B, ATG4C, ATG7 and LGALS3 genes separated the TB and TB-HIV groups, while the ATG9A, IFNA10 and THBD genes separated the LTBI and HIV groups from the others. In experimental conditions, the expression of LC3 showed different levels of LC3 expression in different conditions, while LC3 expression was higher in the condition without stimulation and with Mtb H37Rv infection after 24 hours, this expression was higher after 48 hours. In the condition of cells infected and incubated with rapamycin, it was possible to observe a higher expression of LC3 after 48 hours in the conditions, without infection, infection with M. bovis (BCG) and in the condition of infection with Mtb from the highly prevalent clinical isolate 76937 CONCLUSIONS: The ATG4B, ATG4C, ATG7 and LGALS3 genes were able to separate the active TB and TB-HIV groups from the others, suggesting a relationship between these and active TB, while the ATG9A, IFNA10 and THBD genes were able to separate the groups LTBI and HIV. Mtb virulence factors may influence the development of autophagy, since the LC3 gene has been suggested to have different levels of expression in different Mtb clinical isolates; The time of autophagy induction through rapamycin may influence the different levels of LC3 expression observed in macrophages infected by different mycobacteria.

COMMITTEE MEMBERS:
Externo à Instituição - CÁSSIO SANTANA MEIRA - Senai
Interno - 2236977 - ANTONIO RICARDO KHOURI CUNHA
Externa ao Programa - 2893243 - LUANA LEANDRO GOIS - nullPresidente - ***.852.405-** - THEOLIS COSTA BARBOSA - UFBA
Externa ao Programa - 2205943 - TONYA AZEVEDO DUARTE - null