FRANCIANE MOURADIAN EMIDIO TEIXEIRA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
12 resultados
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- 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.
- 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.
- Severe COVID-19 patients show a dysregulation of the NLRP3 inflammasome in circulating neutrophils(2023) LEAL, Vinicius N. C.; ANDRADE, Milena M. S.; TEIXEIRA, Franciane M. E.; CAMBUI, Raylane A. G.; ROA, Mariela E. G. V.; MARRA, Leticia G.; YAMADA, Suemy M.; ALBERCA, Ricardo W.; GOZZI-SILVA, Sarah C.; YENDO, Tatiana M.; NETTO, Lucas C.; DUARTE, Alberto J. S.; SATO, Maria N.; PONTILLO, AlessandraSARS-CoV-2 triggers inflammasome-dependent release of pro-inflammatory cytokine IL-1 beta and pyroptosis, therefore, contributes to the huge inflammatory response observed in severe COVID-19 patients. Less is known about the engagement of inflammasome in neutrophils, main players in tissue injury and severe infection. We studied the activation of the inflammasome in neutrophils from severe COVID-19 patients and assessed its consequence in term of cells contribution to disease pathogenesis. We demonstrated that NLRP3 inflammasome is dramatically activated in neutrophils from severe COVID-19 patients and that the specific inhibition of NLRP3 reverts neutrophils' activation. Next, the stimulation of severe patients' neutrophils with common NLRP3 stimuli was not able to further activate the inflammasome, possibly due to exhaustion or increased percentage of circulating immature neutrophils. Collectively, our results demonstrate that the NLRP3 inflammasome is hyperactivated in severe COVID-19 neutrophils and its exhaustion may be responsible for the increased susceptibility to subsequent (and possibly lethal) infections. Our findings thus include a novel piece in the complex puzzle of COVID-19 pathogenesis.
- Impact of Inflammatory Immune Dysfunction in Psoriasis Patients at Risk for COVID-19(2021) YENDO, Tatiana Mina; SATO, Maria Notomi; BRANCO, Anna Claudia Calvielli Castelo; PIETROBON, Anna Julia; TEIXEIRA, Franciane Mouradian Emidio; RAMOS, Yasmim alefe Leuzzi; ALBERCA, Ricardo Wesley; VALENCIO, Cesar Giudice; ARRUDA, Vivian Nunes; ROMITI, Ricardo; ARNONE, Marcelo; HIRAYAMA, Andre Luis da Silva; DUARTE, Alberto Jose da Silva; AOKI, Valeria; ORFALI, Raquel LeaoPsoriasis is an immune-mediated dermatosis usually associated with comorbidities. Treatment varies from topicals to systemic drugs and data on susceptibility to viral infections in psoriatic patients are scarce. The objectives of this study were to analyze psoriatic patients on different therapies who were at risk for COVID-19 for seroprevalence of SARS-COV-2, pro-inflammatory cytokine profile, comorbidities and outcomes in order to unveil the immunological mechanisms involved in the anti-viral response in patients with psoriasis. Seventy-five patients with psoriasis were divided according to treatment: immunobiologics, methotrexate, topicals and acitretin. Twenty healthy controls were included. Plasma samples were collected for: IgG SARS-COV-2 (ELISA); IL-27, IL-29 and IL-18 (ELISA); and IL-1 beta, IL-17A, IL-6 and TNF (cytometric array). Seropositivity for SARS-COV-2 was detected in 24 out of 75 psoriasis patients and did not relate to COVID-19 symptoms and/or hospitalization, despite associated comorbidities. Psoriasis patients who were asymptomatic for SARS-COV-2 exhibited immune imbalance with high levels of IL-18, IL-17A and IL-6, and low levels of IL-27 compared to healthy controls. Psoriasis groups showed significant increased cytokine levels only in the group with immunobiologics. Despite immune deviations and lower IL-27, which has a potential antiviral impact, psoriatic patients did not exhibit complications related to COVID-19. An understanding of this kind of proinflammatory profile of psoriatic patients and of the lack of severe outcomes for COVID-19 is essential to establish novel therapeutic approaches and preventive measures, including with regard to the concomitance of viral infections.
- I mmunosenescence and Inflammaging: Risk Factors of Severe COVID-19 in Older People(2020) PIETROBON, Anna Julia; TEIXEIRA, Franciane Mouradian Emidio; SATO, Maria NotomiOld individuals are more susceptible to various infections due to immunological changes that occur during the aging process. These changes named collectively as ""immunosenescence"" include decreases in both the innate and adaptive immune responses in addition to the exacerbated production of inflammatory cytokines. This scenario of immunological dysfunction and its relationship with disease development in older people has been widely studied, especially in infections that can be fatal, such as influenza and, more recently, COVID-19. In the current scenario of SARS-CoV-2 infection, many mechanisms of disease pathogenesis in old individuals have been proposed. To better understand the dynamics of COVID-19 in this group, aspects related to immunological senescence must be well elucidated. In this article, we discuss the main mechanisms involved in immunosenescence and their possible correlations with the susceptibility of individuals of advanced age to SARS-CoV-2 infection and the more severe conditions of the disease.
- 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.
- 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.
- A common variant close to the ""tripwire"" linker region of NLRP1 contributes to severe COVID-19(2023) LEAL, Vinicius N. C.; PAULINO, Leandro M.; CAMBUI, Raylane A. G.; ZUPELLI, Thiago G.; YAMADA, Suemy M.; OLIVEIRA, Leonardo A. T.; DUTRA, Valeria de F.; BUB, Carolina B.; SAKASHITA, Araci M.; YOKOYAMA, Ana Paula H.; KUTNER, Jose M.; VIEIRA, Camila A.; SANTIAGO, Wellyngton M. de S.; ANDRADE, Milena M. S.; TEIXEIRA, Franciane M. E.; ALBERCA, Ricardo W.; GOZZI-SILVA, Sarah C.; YENDO, Tatiana M.; NETTO, Lucas C.; DUARTE, Alberto J. S.; SATO, Maria N.; VENTURINI, James; PONTILLO, AlessandraObjective and design The heterogeneity of response to SARS-CoV-2 infection is directly linked to the individual genetic background. Genetic variants of inflammasome-related genes have been pointed as risk factors for several inflammatory sterile and infectious disease. In the group of inflammasome receptors, NLRP1 stands out as a good novel candidate as severity factor for COVID-19 disease. Methods To address this question, we performed an association study of NLRP1, DPP9, CARD8, IL1B, and IL18 single nucleotide variants (SNVs) in a cohort of 945 COVID-19 patients. Results The NLRP1 p.Leu155His in the linker region, target of viral protease, was significantly associated to COVID-19 severity, which could contribute to the excessive cytokine release reported in severe cases. Conclusion Inflammasome genetic background contributes to individual response to SARS-CoV-2.
- Impact of Retinoic Acid on Immune Cells and Inflammatory Diseases(2018) OLIVEIRA, Luana de Mendonca; TEIXEIRA, Franciane Mouradian Emidio; SATO, Maria NotomiVitamin A metabolite retinoic acid (RA) plays important roles in cell growth, differentiation, organogenesis, and reproduction and a key role in mucosal immune responses. RA promotes dendritic cells to express CD103 and to produce RA, enhances the differentiation of Foxp(3+) inducible regulatory T cells, and induces gut-homing specificity in T cells. Although vitamin A is crucial for maintaining homeostasis at the intestinal barrier and equilibrating immunity and tolerance, including gut dysbiosis, retinoids perform a wide variety of functions in many settings, such as the central nervous system, skin aging, allergic airway diseases, cancer prevention and therapy, and metabolic diseases. The mechanism of RA is interesting to explore as both a mucosal adjuvant and a combination therapy with other effective agents. Here, we review the effect of RA on innate and adaptive immunity with a special emphasis on inflammatory status.
- 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