LUANA DE MENDONCA OLIVEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- LAMP-1 Chimeric to HIV-1 p55Gag in the Immunization of Neonate Mice Induces an Early Germinal Center Formation and AID Expression(2022) TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; PIETROBON, Anna Julia; SALLES, Erika Machado de; LIMA, Maria Regina D'Imperio; VIANA, Isabelle Freire Tabosa; LINS, Roberto Dias; RIGATO, Paula Ordonhez; MARQUES, Ernesto Torres de Azevedo; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiNeonates have a limited adaptive response of plasma cells, germinal center (GC) B cells, and T follicular helper cells (T-FH). As neonatal vaccination can be an important tool for AIDS prevention, these limitations need to be overcome. Chimeric DNA vaccine encoding p55Gag HIV-1 protein conjugated with lysosomal-associated membrane protein 1 (LAMP-1) has been described as immunogenic in the neonate period. Herein, we investigated the immunologic mechanisms involved in neonatal immunization with a LAMP-1/p55Gag (LAMP/Gag) DNA vaccine in a C57BL/6 mouse background. Neonatal LAMP/Gag vaccination induced strong Gag-specific T-cell response until adulthood and elevated levels of anti-Gag IgG antibodies. We also demonstrated for the first time that the immunogenicity of the neonatal period with LAMP/Gag is due to the induction of high-affinity anti-p24 IgG antibodies and long-term plasma cells. Together with that, there is the generation of early TFH cells and the formation of GC sites with the upregulation of activation-induced cytidine deaminase (AID) enzyme mRNA and protein expression in draining lymph nodes after neonatal LAMP/Gag vaccination. These findings underscore that the LAMP-1 strategy in the chimeric vaccine could be useful to enhance antibody production even in the face of neonatal immaturity, and they contribute to the development of new vaccine approaches for other emerging pathogens at an early stage of life.
- 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.
- COVID-19 Disease Course in Former Smokers, Smokers and COPD Patients(2021) ALBERCA, Ricardo Wesley; LIMA, Julia Cataldo; OLIVEIRA, Emily Araujo de; GOZZI-SILVA, Sarah Cristina; RAMOS, Yasmim Alefe Leuzzi; ANDRADE, Milena Mary de Souza; BESERRA, Danielle Rosa; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; PIETROBON, Anna Julia; PEREIRA, Natalli Zanete; TEIXEIRA, Franciane Mouradian Emidio; FERNANDES, Iara Grigoletto; DUARTE, Alberto Jose da Silva; BENARD, Gil; SATO, Maria NotomiThe severe respiratory and systemic disease named coronavirus disease-2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, the COVID-19 pandemic presents a huge social and health challenge worldwide. Many different risk factors are associated with disease severity, such as systemic arterial hypertension, diabetes mellitus, obesity, older age, and other co-infections. Other respiratory diseases such as chronic obstructive pulmonary disease (COPD) and smoking are common comorbidities worldwide. Previous investigations have identified among COVID-19 patients smokers and COPD patients, but recent investigations have questioned the higher risk among these populations. Nevertheless, previous reports failed to isolate smokers and COPD patients without other comorbidities. We performed a longitudinal evaluation of the disease course of smokers, former smokers, and COPD patients with COVID-19 without other comorbidities, from hospitalization to hospital discharge. Although no difference between groups was observed during hospital admission, smokers and COPD patients presented an increase in COVID-19-associated inflammatory markers during the disease course in comparison to non-smokers and former smokers. Our results demonstrated that smoking and COPD are risk factors for severe COVID-19 with possible implications for the ongoing pandemic.
- SARS-CoV-2 Infection and CMV Dissemination in Transplant Recipients as a Treatment for Chagas Cardiomyopathy: A Case Report(2021) GOZZI-SILVA, Sarah Cristina; BENARD, Gil; ALBERCA, Ricardo Wesley; YENDO, Tatiana Mina; TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; BESERRA, Danielle Rosa; PIETROBON, Anna Julia; OLIVEIRA, Emily Araujo de; BRANCO, Anna Claudia Calvielli Castelo; ANDRADE, Milena Mary de Souza; FERNANDES, Iara Grigoletto; PEREIRA, Natalli Zanete; RAMOS, Yasmim Alefe Leuzzi; LIMA, Julia Cataldo; PROVENCI, Bruna; MANGINI, Sandrigo; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has infected over 90 million people worldwide, therefore it is considered a pandemic. SARS-CoV-2 infection can lead to severe pneumonia, acute respiratory distress syndrome (ARDS), septic shock, and/or organ failure. Individuals receiving a heart transplantation (HT) may be at higher risk of adverse outcomes attributable to COVID-19 due to immunosuppressives, as well as concomitant infections that may also influence the prognoses. Herein, we describe the first report of two cases of HT recipients with concomitant infections by SARS-CoV-2, Trypanosoma cruzi, and cytomegalovirus (CMV) dissemination, from the first day of hospitalization due to COVID-19 in the intensive care unit (ICU) until the death of the patients.
- Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients(2022) PIETROBON, Anna Julia; ANDREJEW, Roberta; CUSTODIO, Ricardo Wesley Alberca; OLIVEIRA, Luana de Mendonca; SCHOLL, Juliete Nathali; TEIXEIRA, Franciane Mouradian Emidio; BRITO, Cyro Alves de; GLASER, Talita; KAZMIERSKI, Julia; GOFFINET, Christine; TURDO, Anna Claudia; YENDO, Tatiana; AOKI, Valeria; FIGUEIRO, Fabricio; BATTASTINI, Ana Maria; ULRICH, Henning; BENARD, Gill; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiEctonucleotidases modulate inflammatory responses by balancing extracellular ATP and adenosine (ADO) and might be involved in COVID-19 immunopathogenesis. Here, we explored the contribution of extracellular nucleotide metabolism to COVID-19 severity in mild and severe cases of the disease. We verified that the gene expression of ectonucleotidases is reduced in the whole blood of patients with COVID-19 and is negatively correlated to levels of CRP, an inflammatory marker of disease severity. In line with these findings, COVID-19 patients present higher ATP levels in plasma and reduced levels of ADO when compared to healthy controls. Cell type-specific analysis revealed higher frequencies of CD39+ T cells in severely ill patients, while CD4+ and CD8+ expressing CD73 are reduced in this same group. The frequency of B cells CD39+CD73+ is also decreased during acute COVID-19. Interestingly, B cells from COVID-19 patients showed a reduced capacity to hydrolyze ATP into ADP and ADO. Furthermore, impaired expression of ADO receptors and a compromised activation of its signaling pathway is observed in COVID-19 patients. The presence of ADO in vitro, however, suppressed inflammatory responses triggered in patients' cells. In summary, our findings support the idea that alterations in the metabolism of extracellular purines contribute to immune dysregulation during COVID-19, possibly favoring disease severity, and suggest that ADO may be a therapeutic approach for the disease.
- HIV-I INHIBITION BY IFN-I ADJUVANTS IN NEONATAL MACROPHAGES(2019) PIETROBON, Anna Julia; YOSHIKAWA, Fabio Seiti Yamada; OLIVEIRA, Luana De Mendonca; PEREIRA, Natalli Zanete; SOUZA, Tais Aparecida Matozo De; BARGIERI, Bruna Cunha De Alencar; DUARTE, Alberto Jose Da Silva; SATO, Maria Notomi
- Frequencies of CD33+CD11b+HLA-DR-CD14-CD66b+and CD33+CD11b+HLA-DR-CD14+CD66b-Cells in Peripheral Blood as Severity Immune Biomarkers in COVID-19(2020) ALBERCA, Ricardo Wesley; ANDRADE, Milena Mary de Souza; BRANCO, Anna Claudia Calvielli Castelo; PIETROBON, Anna Julia; PEREIRA, Natalli Zanete; FERNANDES, Iara Grigoletto; OLIVEIRA, Luana de Mendonca; TEIXEIRA, Franciane Mouradian Emidio; BESERRA, Danielle Rosa; OLIVEIRA, Emily Araujo de; GOZZI-SILVA, Sarah Cristina; RAMOS, Yasmim Alefe Leuzzi; BRITO, Cyro Alves de; ARNONE, Marcelo; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCommon clinical features of patients with Coronavirus disease-2019 (COVID-19) vary from fever, to acute severe respiratory distress syndrome. Several laboratory parameters are reported as indicators of COVID-19 severity. We hereby describe the possible novel severity biomarkers for COVID-19, CD11b+CD33+HLA-DR-CD14+ cells and CD11b+CD33+HLA-DR-CD66b+ cells.
- Proinflammatory profile of neonatal monocytes induced by microbial ligands is downmodulated by histamine(2019) BRANCO, Anna Claudia Calvielli Castelo; PEREIRA, Natalli Zanete; YOSHIKAWA, Fabio Seiti Yamada; OLIVEIRA, Luanda Mara da Silva; TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; PIETROBON, Anna Julia; TORREALBA, Marina Passos; LIMA, Josenilson Feitosa de; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiAlthough the neonatal period is characterized by relative immunological immaturity, an inflammatory response due to Toll-like receptor (TLR) activation is observed. Histamine may be one of the factors playing a role in restraining inflammation during the early stages of life. Therefore, we evaluated the responsiveness of human cord blood cells to TLR4 agonists and the immunomodulatory function of histamine in the inflammatory response. Compared with adults, mononuclear cells (MNCs) from newborns (NBs) exhibit impaired production of IFN-gamma-inducible chemokines, such as CXCL10 and CXCL9, upon lipopolysaccharide (LPS) stimulation. Notably, LPS induced a 5-fold increase in CCL2 secretion in NBs. Evaluation of the effect of histamine on LPS-induced CCL2 secretion showed an inhibitory effect in the majority of adults, whereas this effect was detectable in all NBs. Histamine receptor (HR) blockage revealed partial involvement of H1R, H2R and H4R in LPS-induced CCL2 inhibition in MNCs from both NBs and adults. As monocytes are the main type of mononuclear cell that produces CCL2, we evaluated genes related to TLR signaling upon LPS stimulation. Monocytes from NBs showed up-regulation of genes associated with JAK/STAT/NF-kappa B and IFN signaling. Some differentially expressed genes encoding proinflammatory factors were preferentially detected in LPS-activated monocytes from NBs, and markedly down-regulated by histamine. The immunomodulatory role of histamine on CCL2 and CXCL8 was detected at the transcript and protein levels. Our findings show that NBs have enhanced CCL2 responsiveness to LPS, and that histamine acts in immune homeostasis during the neonatal period to counterbalance the robustness of TLR stimulation.
- Maternal-Fetal Interplay in Zika Virus Infection and Adverse Perinatal Outcomes(2020) TEIXEIRA, Franciane Mouradian Emidio; PIETROBON, Anna Julia; OLIVEIRA, Luana de Mendonca; OLIVEIRA, Luanda Mara da Silva; SATO, Maria NotomiDuring pregnancy, the organization of complex tolerance mechanisms occurs to assure non-rejection of the semiallogeneic fetus. Pregnancy is a period of vulnerability to some viral infections, mainly during the first and second trimesters, that may cause congenital damage to the fetus. Recently, Zika virus (ZIKV) infection has gained great notoriety due to the occurrence of congenital ZIKV syndrome, characterized by fetal microcephaly, which results from the ability of ZIKV to infect placental cells and neural precursors in the fetus. Importantly, in addition to the congenital effects, studies have shown that perinatal ZIKV infection causes a number of disorders, including maculopapular rash, conjunctivitis, and arthralgia. In this paper, we contextualize the immunological aspects involved in the maternal-fetal interface and vulnerability to ZIKV infection, especially the alterations resulting in perinatal outcomes. This highlights the need to develop protective maternal vaccine strategies or interventions that are capable of preventing fetal or even neonatal infection.