Banca de DEFESA: SCARLET TORRES MORAES MOTA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : SCARLET TORRES MORAES MOTA
DATE: 28/10/2022
TIME: 14:00
LOCAL: IGM Sala Virtual 5
TITLE:

Transcriptional signatures associated with BCG vaccination and RAB11A modulation in tuberculosis

KEY WORDS:

tuberculosis, BCG, gene expression, RAB11

PAGES: 124
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Tuberculosis (TB) is a chronic infectious disease difficult to manage and the
mechanisms involved in disease progression are not fully established. The gene
expression profile has been studied with the objective of validating potential
biomarkers that help in the understanding of the processes involved in TB and in the
development of strategies against disease. Vaccination with BCG has been pointed
out with the possibility of modulating the host response and its efficacy against TB
has been widely discussed, but it is still not fully known about what these effects
would be and their duration in the organism. Through a meta-analysis of
transcriptome data using GEO repository, we were able to demonstrate that
vaccination with BCG is capable of generating lasting effects in the host affecting the
modulation of specific genes. When comparing the groups of uninfected, infected and
sick that were unvaccinated, 100 genes were observed (92 down-regulated and 8
up-regulated), mainly associated with pathways and functions linked to metabolism.
Among vaccinated individuals, comparing the same groups, 53 genes were
observed, being 18 overexpressed and 35 underexpressed, mainly linked to
immunity processes. In a secondary meta-analysis, we also found distinct
vaccine-linked signatures, with 5 underexpressed genes identified for the vaccinated
and 2 genes (1 over and 1 underexpressed) for the unvaccinated. Our results also
showed that a gene of the Rab11 subfamily (composed of two other members of high
homology, RAB11A and RAB11B), RAB25, was overexpressed in sick individuals
unvaccinated with BCG, when also compared sick individuals, but vaccinated. During
our evaluations, we identified RAB11A as the target of our study. In whole blood
samples from a cohort of patients with active tuberculosis from our population, we
observed higher mean expression values for the RAB11A gene in sick and
unvaccinated individuals compared to vaccinated, corroborating the meta-analysis
data. We also saw that the expression values of this gene are lower in THP-1 cells
infected with BCG strain compared to uninfected. For future investigation of the role
of this gene, we successfully performed gene silencing in THP-1 cells using RNA
interference methodology. With this work, we were able to identify the transcriptional
signatures associated with BCG vaccination and point out a target that deserves to
be better studied in tuberculosis.

COMMITTEE MEMBERS:
Interno - ***.442.755-** - BRUNO DE BEZERRIL ANDRADE - UFBA
Interna - ***.952.725-** - NATALIA MACHADO TAVARES - UFBA
Externo à Instituição - PABLO IVAN PEREIRA RAMOS - Fiocruz-Ba
Externo ao Programa - 2983099 - RYAN DOS SANTOS COSTA - nullPresidente - ***.852.405-** - THEOLIS COSTA BARBOSA - UFBA