LUANA DE MENDONCA OLIVEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
Agora exibindo 1 - 3 de 3
- Generation of Cytotoxic T Cells and Dysfunctional CD8 T Cells in Severe COVID-19 Patients(2022) GOZZI-SILVA, Sarah Cristina; OLIVEIRA, Luana de Mendonca; ALBERCA, Ricardo Wesley; PEREIRA, Natalli Zanete; YOSHIKAWA, Fabio Seiti; PIETROBON, Anna Julia; YENDO, Tatiana Mina; ANDRADE, Milena Mary de Souza; RAMOS, Yasmim Alefe Leuzzi; BRITO, Cyro Alves; OLIVEIRA, Emily Araujo; BESERRA, Danielle Rosa; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCOVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The viral infection can evolve asymptomatically or can generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia based on the severity of symptoms in patients affected with COVID-19 is frequent. However, the profiles of CD4+ and CD8+ T cells regarding cytotoxicity and antiviral factor expression have not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study was to evaluate the phenotypic and functional profile of T lymphocytes in patients with moderate and severe/critical COVID-19. During the pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Notwithstanding lymphopenia, we observed an increase in the expression of CD28, a co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T lymphocytes as well as an increase in the frequency of CD4+ T cells, CD8+ T cells, and NK cells that express the immunological checkpoint protein PD-1 in patients with a severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T cells was already observed at the baseline level and scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T lymphocytes decreased the cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed by t-SNE, there were CD4+ T-cytotoxic and CD8+ T with low granzyme production, evidencing their dysfunction in severe/critical conditions. In addition, purified CD8+ T lymphocytes from patients with severe COVID-19 showed increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and, curiously, had reduced expression of TNF-alpha. The cytotoxic profile of CD4+ T cells may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T cells and CD8+ T cells in the severity of acute COVID-19 infection.
- Upregulation of PD-1 Expression and High sPD-L1 Levels Associated with COVID-19 Severity(2022) BESERRA, Danielle Rosa; ALBERCA, Ricardo Wesley; BRANCO, Anna Claudia Calvielli Castelo; OLIVEIRA, Luana de Mendonca; ANDRADE, Milena Mary de Souza; GOZZI-SILVA, Sarah Cristina; TEIXEIRA, Franciane Mouradian Emidio; YENDO, Tatiana Mina; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCOVID-19 has several mechanisms that can lead to lymphocyte depletion/exhaustion. The checkpoint inhibitor molecule programmed death protein 1 (PD-1) and its programmed death-ligand 1 (PDL-1) play an important role in inhibiting cellular activity as well as the depletion of these cells. In this study, we evaluated PD-1 expression in TCD4+, TCD8+, and CD19+ lymphocytes from SARS-CoV-2-infected patients. A decreased frequency of total lymphocytes and an increased PD-1 expression in TCD4+ and CD19+ lymphocytes were verified in severe/critical COVID-19 patients. In addition, we found a decreased frequency of total monocytes with an increased PD-1 expression on CD14+ monocytes in severe/critical patients in association with the time of infection. Moreover, we observed an increase in sPD-L1 circulant levels associated with the severity of the disease. Overall, these data indicate an important role of the PD-1/PDL-1 axis in COVID-19 and may provide a severity-associated biomarker and therapeutic target during SARS-CoV-2 infection.
- Resveratrol Downmodulates Neutrophil Extracellular Trap (NET) Generation by Neutrophils in Patients with Severe COVID-19(2022) ANDRADE, Milena M. de Souza; LEAL, Vinicius N. C.; FERNANDES, Iara G.; GOZZI-SILVA, Sarah C.; BESERRA, Danielle R.; OLIVEIRA, Emily A.; TEIXEIRA, Franciane M. E.; YENDO, Tatiana M.; SOUSA, Maria da Gloria T.; TEODORO, Walcy R.; OLIVEIRA, Luana de M.; ALBERCA, Ricardo W.; AOKI, Valeria; DUARTE, Alberto J. S.; SATO, Maria N.The formation of microthrombi in lung autopsies indicates the involvement of NETs in the immunopathogenesis of severe COVID-19. Therefore, supplements inhibiting NET formation, in association with drugs with fewer adverse effects, should be a relevant strategy to attenuate the disease. Resveratrol (RESV) is a natural polyphenol with an important antiviral and antioxidant role. To modulate neutrophils from patients infected with SARS-CoV-2, we evaluated the in vitro effect of RESV on NET formation. Herein, we investigated 190 patients hospitalized with moderate, severe, and critical symptoms at Hospital das Clinicas, Brazil. We observed that neutrophilia in patients with severe COVID-19 infection is composed of neutrophils with activated profile able to release NET spontaneously. Notably, RESV decreased the neutrophil-activated status and the release of free DNA, inhibiting NET formation even under the specific PMA stimulus. At present, there is no evidence of the role of RESV in neutrophils from patients with COVID-19 infection. These findings suggest that adjunctive therapies with RESV may help decrease the inflammation of viral or bacterial infection, improving patient outcomes.