LUANA DE MENDONCA OLIVEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants(2024) TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; ALBERCA, Ricardo Wesley; SOUSA, Emanuella Sarmento Alho de; LEITE, Bruno Henrique de Sousa; ADAN, Wenny Camilla dos Santos; DUARTE, Alberto Jose da Silva; LINS, Roberto Dias; SATO, Maria Notomi; VIANA, Isabelle Freire TabosaZika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_Delta STP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_Delta STP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-Delta STP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_Delta STP+Alum protected adult mice upon viral challenge. Collectively, the ZK_Delta STP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies.
- 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.
- Physical Exercise Induces Immunoregulation of TREG, M2, and pDCs in a Lung Allergic Inflammation Model(2019) FERNANDES, Paula; OLIVEIRA, Luana de Mendonca; BRUGGEMANN, Thayse Regina; SATO, Maria Notomi; OLIVO, Clarice Rosa; ARANTES-COSTA, Fernanda MagalhaesThe benefits of moderate aerobic physical exercise for allergic asthma are well-known, particularly that of the anti-inflammatory effect that occurs by reducing Th2 responses and lung remodeling. However, the mechanisms of this immunoregulation are still under investigation. In this study, we investigated the possible immunoregulatory mechanisms of lung inflammation induced by moderate aerobic exercise in an experimental asthma model. BALB/c mice were distributed into Control, Exercise (EX), OVA, and OEX groups. OVA and OEX groups were sensitized with ovalbumin (OVA) on days 0, 14, 21, 28, and 42 and were challenged with OVA aerosol three times a week from days 21 to 51. The EX and OEX groups underwent moderate aerobic physical exercise from days 21 to 51 (5 d/w, 1 h/d). The mice were euthanized on day 52. We evaluated pulmonary cytokine production, serum immunoglobulin levels, and the inflammatory cell profile in lung and mediastinal lymph nodes. OVA mice showed increased expression of IL-4, IL-6, IL-10, and TGF-beta and decreased macrophage type 2 (M2) recruitment. Physical exercise did not affect the increased antibody production of IgG2a, IgG1, or IgE induced by OVA. Of note, physical exercise alone markedly increased production of anti-inflammatory cytokines such as IL-10 and TGF-beta. Physical exercise in OVA-mice also increased the recruitment of M2 in the lungs, as well as the influx and activation of regulatory T cells (Tregs) and CD4 and CD8 lymphocytes. In the draining lymph nodes, it was also observed that physical exercise increased the activation of CD4 T cells, regardless of the presence of OVA. Notably, physical exercise decreased common dendritic cells' (cDCs; pro-inflammatory) expression of co-stimulatory molecules such as CD80, CD86, and ICOSL in the draining lymph nodes, as well as increased ICOSL in plasmacytoid dendritic cells (pDCs; anti-inflammatory). Together, these findings show that physical exercise modulates pulmonary allergic inflammation by increasing Treg and M2 recruitment, as well as pDCs activation, which leads to an increase in anti-inflammatory cytokines and a decrease in pro-inflammatory cells and mediators.
- Cigarette Smoke Increases CD8 alpha(+) Dendritic Cells in an Ovalbumin-Induced Airway Inflammation(2017) BRUGGEMANN, Thayse Regina; FERNANDES, Paula; OLIVEIRA, Luana de Mendonca; SATO, Maria Notomi; MARTINS, Milton de Arruda; ARANTES-COSTA, Fernanda MagalhaesAsthma is an allergic lung disease and, when associated to cigarette smoke exposition, some patients show controversial signs about lung function and other inflammatory mediators. Epidemiologic and experimental studies have shown both increasing and decreasing inflammation in lungs of subjects with asthma and exposed to cigarette smoke. Therefore, in this study, we analyzed how cigarette smoke affects pro-inflammatory and anti-inflammatory mediators in a murine model of allergic pulmonary inflammation. We sensitized Balb/c mice to ovalbumin (OVA) with two intraperitoneal injections. After sensitization, the animals were exposed to cigarette smoke twice a day, 30 min per exposition, for 12 consecutive days. In order to drive the cell to the lungs, four aerosol challenges were performed every 48 h with the same allergen of sensitization. OVA sensitization and challenge developed pulmonary Th2 characteristic response with increased airway responsiveness, remodeling, increased levels of IgE, interleukin (IL)-4, and IL-13. Cigarette smoke, unexpectedly, reduced the levels of IL-4 and IL-13 and simultaneously decreased anti-inflammatory cytokines as IL-10 and transforming growth factor (TGF)-alpha in sensitized and challenged animals. OVA combined with cigarette smoke exposition decreased the number of eosinophils in bronchoalveolar lavage and increased the number of neutrophils in lung. The combination of cigarette smoke and lung allergy increased recruitment of lymphoid dendritic cells (DCs) into lymph nodes, which may be the leading cause to an increase in number and activation of CD8(+) T cells in lungs. In addition, lung allergy and cigarette smoke exposure decreased an important regulatory subtype of DC such as plasmacytoid DC as well as its activation by expression of CD86, PDL2, and ICOSL, and it was sufficient to decrease T regs influx and anti-inflammatory cytokines release such as IL-10 and TGF-alpha but not enough to diminish the structural changes. In conclusion, we observed, in this model, that OVA sensitization and challenge combined with cigarette smoke exposure leads to mischaracterization of the Th2 response of asthma by decreasing the number of eosinophils, IL-4, and IL-13 and increasing number of neutrophils, which is related to the increased number of CD8 alpha(+) DCs and CD8+ T cells as well as reduction of the regulatory cells and its released cytokines.
- Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants (vol 15, 1307546, 2024)(2024) TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; ALBERCA, Ricardo Wesley; SOUSA, Emanuella Sarmento Alho de; LEITE, Bruno Henrique de Sousa; ADAN, Wenny Camilla dos Santos; DUARTE, Alberto Jose da Silva; LINS, Roberto Dias; SATO, Maria Notomi; VIANA, Isabelle Freire Tabosa
- 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.