MARIA NOTOMI SATO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Dermatologia, Faculdade de Medicina - Docente
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina - Líder
38 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 38
- Mucosal and systemic anti-GAG immunity induced by neonatal immunization with HIV LAMP/gag DNA vaccine in mice(2011) GOLDONI, Adriana Leticia; MACIEL JR., Milton; RIGATO, Paula Ordonhez; PIUBELLI, Orlando; BRITO, Cyro Alves de; MELO, Andrea; MARQUES, Ernesto Torres; AUGUST, Joseph Thomas; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiVaccines capable of inducing mucosal immunity in early postnatal life until adulthood, protecting early sexual initiation, should be considered as strategies to vaccination against HIV. The HIV-1 GAG protein as a chimera with the lysosome-associated membrane protein (LAMP/gag), encoded by a DNA vaccine, is targeted to the endosomal/lysosomal compartment that contains class II MHC molecules and has been shown to be immunogenic in adult mice. Assuming that one such strategy could help to overcome the immunological immaturity in the early postnatal period, we have evaluated the systemic and mucosal immunogenicity of LAMP/gag immunization in neonatal mice. Intranasal immunization with LAMP/gag vaccine induced higher levels of sIgA and IgG anti-GAG antibodies in intestinal washes than did the gag vaccine. The combination of ID injections and the IN protocol with the chimeric vaccine promoted the increase of Ab levels in sera. Both vaccines induced splenic IFN-gamma- secreting cells against GAG peptide pools, as well as in vivo cytotoxic T lymphocyte (CTL) function, and increased the percentage of CD8+ T cells to the immunodominant class I peptide in gut and spleen. However, only the chimeric vaccine was able to enhance Th1/Th2 cytokine secretion in response to class II GAG peptide and to enhance IL-4-secreting cells against GAG peptides and p24 protein stimuli. Long-lasting humoral and cellular responses were detected until adult age, following neonatal immunization with the chimeric vaccine. The LAMP/gag vaccination was able to induce potent GAG-specific T and B cell immune responses in early life which are essential to elicit sustained and long-lasting mucosal and systemic humoral response.
- Up-regulation of chemokine C-C ligand 2 (CCL2) and C-X-C chemokine 8 (CXCL8) expression by monocytes in chronic idiopathic urticaria(2012) SANTOS, J. C.; BRITO, C. A. de; FUTATA, E. A.; AZOR, M. H.; ORII, N. M.; MARUTA, C. W.; RIVITTI, E. A.; DUARTE, A. J. S.; SATO, M. N.The disturbed cytokinechemokine network could play an important role in the onset of diseases with inflammatory processes such as chronic idiopathic urticaria (CIU). Our main objectives were to evaluate the relation between proinflammatory chemokine serum levels from CIU patients and their response to autologous skin test (ASST) and basophil histamine release (BHR). We also aimed to assess the chemokine secretion by peripheral blood mononuclear cells (PBMC) upon polyclonal stimulus and to evaluate chemokine CC ligand 2/C-X-C chemokine 8 (CCL2/CXCL8) and Toll-like receptor-4 (TLR-4) expression in monocytes. We observed significantly higher serum levels of the CXCL8, CXCL9, CXCL10 and CCL2 in CIU patients compared to the healthy group, regardless of the BHR or ASST response. The basal secretion of CCL2 by PBMC or induced by Staphylococcus aureus enterotoxin A (SEA) was higher in CIU patients than in the control group, as well as for CXCL8 and CCL5 secretions upon phytohaemagglutinin stimulation. Also, up-regulation of CCL2 and CXCL8 mRNA expression was found in monocytes of patients upon SEA stimulation. The findings showed a high responsiveness of monocytes through CCL2/CXCL8 expression, contributing to the creation of a proinflammatory environment in CIU.
- 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.
- Immunity in the spleen and blood of mice immunized with irradiated Toxoplasma gondii tachyzoites(2016) ZORGI, Nahiara Esteves; GALISTEO JR., Andres Jimenez; SATO, Maria Notomi; NASCIMENTO, Nanci do; ANDRADE JR., Heitor Franco deToxoplasma gondii infection induces a strong and long-lasting immune response that is able to prevent most reinfections but allows tissue cysts. Irradiated, sterilized T. gondii tachyzoites are an interesting vaccine, and they induce immunity that is similar to infection, but without cysts. In this study, we evaluated the cellular immune response in the blood and spleen of mice immunized with this preparation by mouth (v.o.) or intraperitoneally (i.p.) and analyzed the protection after challenge with viable parasites. BALB/c mice were immunized with three i.p. or v.o. doses of irradiated T. gondii tachyzoites. Oral challenge with ten cysts of the ME-49 or VEG strain at 90 days after the last dose resulted in high levels of protection with low parasite burden in the immunized animals. There were higher levels of specific IgG, IgA and IgM antibodies in the serum, and the i.p. immunized mice had higher levels of the high-affinity IgG and IgM antibodies than the orally immunized mice, which had more high-affinity IgA antibodies. B cells (CD19(+)), plasma cells (CD138(+)) and the CD4(+) and CD8(+) T cell populations were increased in both the blood and spleen. Cells from the spleen of the i.p. immunized mice also showed antigen-induced production of interleukin-10 (IL-10), interferon gamma (IFN-gamma) and interleukin 4 (IL-4). The CD4(+) T cells, B cells and likely CD8(+) T cells from the spleens of the i.p. immunized mice proliferated with a specific antigen. The protection was correlated with the spleen and blood CD8(+) T cell, high-affinity IgG and IgM and antigen-induced IL-10 and IL-4 production. Immunization with irradiated T. gondii tachyzoites induces an immune response that is mediated by B cells and CD4(+) and CD8(+) T cells, with increased humoral and cellular immune responses that are necessary for host protection after infection. The vaccine is similar to natural infection, but free of tissue cysts; this immunity restrains infection at challenge and can be an attractive and efficient model for vaccine development in toxoplasmosis.
- Tolerogenic microenvironment in neonatal period induced by maternal immunization with ovalbumin(2014) MUNIZ, Bruno Pacola; VICTOR, Jefferson Russo; OLIVEIRA, Luana de Mendonca; LIRA, Aline Aparecida de Lima; PERINI, Adenir; OLIVO, Clarice Rosa; ARANTES-COSTA, Fernanda Magalhaes; MARTINS, Milton Arruda; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiMaternal immunization with allergens, such as ovalbumin (OVA), can inhibit the development of an allergic response in offspring. The regulatory mechanisms seem to be mediated by maternal antibodies (MatAbs) and factors generated by the maternal fetal interface. The aim of this study was to verify the pathways of inhibitory Ab transference after maternal immunization with OVA and the effect of the offspring's dendritic cells (DCs) on the generation of regulatory T (Treg) cells. We verified that preconceptional OVA immunization induces high levels of proinflammatory and regulatory cytokines in the amniotic fluid, allowing the transference of high levels of anti-OVA IgG1 Abs to the offspring. Using an adoptive nursing protocol, we verified that maternal immunization leads to MatAb transference by the placental route and by breastfeeding contribute to the inhibition of anaphylactic IgE and IgG1 Ab responses in immunized offspring. We observed that maternal immunization decreased eosinophil numbers in recovered bronchoalveolar lavage fluid and in the lung tissue, whereas with a lack of control of airway responsiveness to methacholine. Maternal immunization induced in young offspring a decreased percentage of CD11c+ DCs expressing MHC class II and CD40 molecules. Moreover, DCs from both groups of offspring when pulsed with OVA, were able to induce Treg cells in vitro. Similarly, OVA immunization at the neonatal stage increased the frequency of Treg cells, regardless of the mother's immunization status. These findings emphasize that maternal immunization leads to a complex interaction of regulatory factors, with MatAbs, DCs and Treg cells affecting the tolerance of offspring during an allergic response.
- Role of Histamine in Modulating the Immune Response and Inflammation(2018) BRANCO, Anna Claudia Calvielli Castelo; YOSHIKAWA, Fabio Seiti Yamada; PIETROBON, Anna Julia; SATO, Maria NotomiInflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, and leukotrienes, impact the immune system, usually as proinflammatory factors. Other mediators act as regulatory components to establish homeostasis after injury or prevent the inflammatory process. Histamine, a biogenic vasoactive amine, causes symptoms such as allergies and has a pleiotropic effect that is dependent on its interaction with its four histamine receptors. In this review, we discuss the dualistic effects of histamine: how histamine affects inflammation of the immune system through the activation of intracellular pathways that induce the production of inflammatory mediators and cytokines in different immune cells and how histamine exerts regulatory functions in innate and adaptive immune responses. We also evaluate the interactions between these effects.
- Chemokine, cytokine and type I interferon production induced by Toll-like receptor activation in common variable immune deficiency(2016) LOLLO, Camila de; VASCONCELOS, Dewton de Moraes; OLIVEIRA, Luanda Mara da Silva; DOMINGUES, Rosana; CARVALHO, Gabriel Costa de; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCommon variable immunodeficiency (CVID) is the most common symptomatic primary antibody deficiency and is associated with recurrent infections and chronic inflammatory diseases. We evaluated the ability of Toll-like receptor (TLR) ligands to induce secretion of chemokines, cytokines and type I interferons by peripheral blood mononuclear cells (PBMCs) from CVID patients. High levels of CXCL10, CCL2, CXCL9, CCL5, CXCL8, and IL-6 were detected in sera of CVID patients compared with healthy controls. Increased chemokine levels were observed in unstimulated PBMCs, but after stimulation with TLR2 and TLR4 agonists, equivalent chemokine and pro-inflammatory cytokine secretion, as in healthy controls, was observed, whereas TLR4 agonist induced a decreased secretion of CCL2 and CXCL8 and increased secretion of TNF. Decreased IFN-alpha secretion induced by TLR7/TLR8 activation was observed in CVID, which was recovered with TLR9 signaling. Our findings revealed that TLR9 activation has an adjuvant effect on the altered type I response in CVID.
- Effect of exercise training on Treg cell response in severe COPD individuals: a randomized and controlled trial(2022) ITO, J. T.; OLIVEIRA, L. M.; V, L. Alves; XAVIER, R. F.; SATO, M. N.; CARVALHO, C. R. F.; TIBERIO, I. F. L. C.; LOPES, F. D. T. Q. S.
- 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.
- Constant-Load Exercise Versus High-Intensity Interval Training on Aerobic Fitness in Moderate-to-Severe Asthma: A Randomized Controlled Trial(2022) SILVA, Ronaldo Aparecido da; STELMACH, Rafael; OLIVEIRA, Luanda Mara da Silva; SATO, Maria Notomi; CUKIER, Alberto; CARVALHO, Celso Ricardo FernandesBACKGROUND: The effects of high-intensity interval training (HIIT) on dyspnea and aerobic fitness in adults with asthma are poorly understood. OBJECTIVE: To compare constant-load exercise (CLE) versus HIIT for improvements in dyspnea symptoms and clinical control in adults with moderate-to-severe asthma. METHODS: Participants were randomized into 2 groups: CLE (n = 27; started with 70% of maximal watts [Wmax] obtained during cardiopulmonary exercise testing [CPET]) and HIIT (n = 28; started with 80% and increased until 140% Wmax). Exercise training lasted 12 weeks (twice/week, 40 minutes/ session on a cycle ergometer), and the intensity was based on CPET. Clinical asthma control (Asthma Control Questionnaire), aerobic fitness (the peak of oxygen uptake), health-related quality of life (Asthma Quality of Life Questionnaire), physical activity levels (PAL; accelerometer), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale questionnaire), and dyspnea were evaluated before and after the intervention. Systemic and airway inflammation were also assessed. Two-way analysis of variance and chi(2) tests were used for comparisons. Sixteen participants dropped out during the interventions and returned for the final evaluations. RESULTS: The CLE and HIIT groups showed similar improvements in aerobic fitness. The HIIT group had lower dyspnea and fatigue perception scores and higher PAL than the CLE group (P < .05) and clinical improvements in the psychosocial distress. In addition, only the HIIT group achieved a minimal clinically important difference in asthma symptoms. There was no change in the systemic and airway inflammation (P > .05). CONCLUSION: Both interventions promoted similar improvements in aerobic fitness; however, HIIT induced a greater reduction in dyspnea and fatigue perception. Similar responses were observed for other variables. (C) 2022 American Academy of Allergy, Asthma & Immunology