Banca de DEFESA: PAULO SÉRGIO DE MORAIS DA SILVEIRA MATTOS

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : PAULO SÉRGIO DE MORAIS DA SILVEIRA MATTOS
DATE: 29/04/2022
TIME: 09:00
LOCAL: IGM Sala Virtual 5
TITLE:

Dynamics between CD4+ T lymphocytes and the different clinical presentations of tuberculosis

KEY WORDS:

Tuberculosis, CD4+ T cells, HIV, biomarker.

PAGES: 80
BIG AREA: Ciências Biológicas
AREA: Parasitologia
SUMMARY:

ABSTRACT
INTRODUCTION: The diagnosis of tuberculosis (TB) is performed by means of the detection of M. tuberculosis (MTB) in microbiological tests, such as smear and culture and molecular biology assays. The interpretation of these tests is limited, as they do not provide information on the systemic, cellular, and inflammatory repercussions and they have low sensitivity in paucibacillary individuals. OBJECTIVE: To evaluate cell activation and phenotypic changes in CD4+ T lymphocytes in individuals with tuberculosis, with or without HIV. METHODS: Initially, in a cohort from Brazil, the use of CD38, HLADR and/or Ki67 cell activation markers on MTB-specific CD4+ T cells to discriminate pulmonary tuberculosis (PTB) from extrapulmonary tuberculosis (EPTB) from latent tuberculosis infection (LTBI), as well as EPTB from PTB, was validated. We also tested the effect of HIV coinfection on diagnostic performance. Added to this thesis, another manuscript covering South Indian patients with TB-HIV before and after initiation of ART, determining the phenotypic changes in CD4+ T cells during Tuberculosis-immune reconstitution inflammatory (SIRI) and their relationship with systemic inflammation. In this study, we analyzed subpopulations of T lymphocytes and biomarkers in peripheral blood. RESULTS: EPTB and PTB patients had a higher frequency of T CD4+ IFN-γ+ cells expressing CD38, HLADR compared to LTBI. Furthermore, the frequencies of HLADR+ or Ki67+ cells accurately distinguished EPTB from PTB. HIV infection did not affect the ability of these markers to distinguish active tuberculosis from LTBI or EPTB from PTB. In the second study, the frequency of naive CD4 T cells (CD27+CD45RO−), as well as of effector memory (CD27−CD45RO+) distinguished individuals who developed the inflammatory reconstitution syndrome from those who did not, in the 2nd-6th week after starting ART. Further analysis revealed that ART reconstituted different amounts of subsets of CD4+ T lymphocytes with preferential expansion of CXCR3+ CCR6− cells in TB-SIRI patients. In addition, there was an expansion and functional restoration of CXCR3−CCR6 CD4+ lymphocytes expressing central memory markers (CD27+ CD45RO+) and corresponding cytokines, with a reduction in CXCR3−CCR6+ cells after ART only in those who developed TB-SIRI. CONCLUSION: Cell activation markers on CD4+ T cells specific for MTB distinguished active TB from LTBI and EPTB from PTB, regardless of HIV infection status. CD4+ T cell subsets are strongly associated with SIRI.

BANKING MEMBERS:
Presidente - 803.442.755-15 - BRUNO DE BEZERRIL ANDRADE - UFBA
Externo à Instituição - JORGE CLARENCIO SOUZA ANDRADE - Fiocruz-Ba
Externa à Instituição - LUKARY OLIVEIRA TAKENAMI
Interno - 804.709.555-20 - RICARDO RICCIO OLIVEIRA - UFBA
Externa à Instituição - TONYA AZEVEDO DUARTE - UFRJ