MARIA NOTOMI SATO

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Departamento de Dermatologia, Faculdade de Medicina - Docente
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina - Líder

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Autor e Coautores FMUSP-HC Normalizados: LUANDA MARA DA SILVA OLIVEIRA ×

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Agora exibindo 1 - 10 de 24
  • article 8 Citação(ões) na Scopus
    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 Notomi
    Common 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.
  • article 18 Citação(ões) na Scopus
    Staphylococcal enterotoxins modulate the effector CD4(+)T cell response by reshaping the gene expression profile in adults with atopic dermatitis
    (2019) ORFALI, Raquel Leao; YOSHIKAWA, Fabio Seiti Yamada; OLIVEIRA, Luanda Mara da Silva; PEREIRA, Natalli Zanete; LIMA, Josenilson Feitosa de; RAMOS, Yasmim Alefe Leuzzi; DUARTE, Alberto Jose da Silva; SATO, Maria Notomi; AOKI, Valeria
    Staphylococcus aureus colonizes the skin of atopic dermatitis (AD) individuals, but the impact of its enterotoxins on the chronic activation of CD4(+)T cells demands further analysis. We aimed to analyze the CD4(+)T cell anergy profile and their phenotypic and functional features through differential expression of cellular activation markers, cytokine production and response to staphylococcal enterotoxin A (SEA). A panel of 84 genes relevant to T cell anergy was assessed by PCR array in FACS-sorted CD4(+)T cells, and the most prominent genes were validated by RT-qPCR. We evaluated frequencies of circulating CD4(+)T cells secreting single or multiple (polyfunctional) cytokines (IL-17A, IL-22, TNF, IFN-gamma, and MIP-1 beta) and expression of activation marker CD38 in response to SEA stimulation by flow cytometry. Our main findings indicated upregulation of anergy-related genes (EGR2 and IL13) promoted by SEA in AD patients, associated to a compromised polyfunctional response particularly in CD4(+)CD38(+)T cells in response to antigen stimulation. The pathogenic role of staphylococcal enterotoxins in adult AD can be explained by their ability to downmodulate the activated effector T cell response, altering gene expression profile such as EGR2 induction, and may contribute to negative regulation of polyfunctional CD4(+)T cells in these patients.
  • article 9 Citação(ões) na Scopus
    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 Fernandes
    BACKGROUND: 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
  • article 20 Citação(ões) na Scopus
    Distinct Natural Killer Cells in HIV-Exposed Seronegative Subjects With Effector Cytotoxic CD56(dim) and CD56(bright) Cells and Memory-Like CD57(+)NKG2C(+)CD56(dim) Cells
    (2014) LIMA, Josenilson F.; OLIVEIRA, Luanda M. S.; PEREIRA, Natalli Z.; MITSUNARI, Gabrielle E.; DUARTE, Alberto J. S.; SATO, Maria N.
    Background: Innate immunity, including natural killer (NK) cells, may play a significant role in maintaining natural resistance to infection in highly HIV-exposed seronegative (HESN) subjects. The differences between NK-cell subsets, regarding their activating/maturing marker expression and their memory markers, in HESN subjects are not fully defined. Methods: We have conducted an analysis of the activating/memory markers and intracellular CD107a and interferon gamma (IFN-gamma) expression in NK-cell subsets from HESN and HIV-infected and healthy subjects. Results: HESN individuals showed an increased expression of activating markers, such as NKG2D in CD56(bright) and CD56(dim) NK cells, and an increased frequency of CD56(bright)CD127(+) and fully mature CD56(dim)CD57(+) NK cells compared with HIV-infected patients and healthy control subjects. Of note, HESN individuals showed an increased frequency of memory CD56(dim)CD57(+) NK cells, and this is known to be expanded on cytomegalovirus infection, as evidenced by their high rate of cytomegalovirus seropositivity. Simultaneous expression of the CD94, NKG2A, NKG2C, and NKG2D receptors on CD56(bright) NK cells was detected in HESN subjects, whereas in the HIV-1 group, the expression of these 4 receptors was enhanced in CD56(dim) NK cells. It was also found that CD56(bright) and CD56(dim) NK cells in HESN subjects showed increased CD107a and/or IFN-g expression. Conclusions: The NK cells from HESN individuals presented a unique activation profile, with increased expression of NKG2D, CD107a, and IFN-g and ""memory"" CD57(+) CD56(dim) NK cells. The complex network of functional NK-cell activities in HESN individuals may be exploited for long-term protection through vaccination.
  • article 11 Citação(ões) na Scopus
    Zika Virus Infects Newborn Monocytes Without Triggering a Substantial Cytokine Response
    (2019) YOSHIKAWA, Fabio Seiti Yamada; PIETROBON, Anna Julia; BRANCO, Anna Claudia Calvielli Castelo; PEREIRA, Natalli Zanete; OLIVEIRA, Luanda Mara da Silva; MACHADO, Clarisse Martins; DUARTE, Alberto Jose da Silva; SATO, Maria Notomi
    Zika virus (ZIKV) is a clinically important flavivirus that can cause neurological disturbances in newborns. Here, we investigated comparatively the outcome of in vitro infection of newborn monocytes by ZIKV. We observed that neonatal cells show defective production of interleukin 1 beta, interleukin 10, and monocyte chemoattractant protein 1 in response to ZIKV, although they were as efficient as adult cells in supporting viral infection. Although CLEC5A is a classical flavivirus immune receptor, it is not essential to the cytokine response, but it regulates the viral load only in adult cells. Greater expression of viral entry receptors may create a favorable environment for viral invasion in neonatal monocytes. We are the first to suggest a role for CLEC5A in human monocyte infectivity and to show that newborn monocytes are interesting targets in ZIKV pathogenesis, owing to their ability to carry the virus with only a partial triggering of the immune response, creating a potentially favorable environment for virus-related pathologies in young individuals.
  • conferenceObject
    Staphylococcus aureus enterotoxins modulate IL-22-secreting cells in adults with atopic dermatitis
    (2018) ORFALI, R. L.; OLIVEIRA, L. M. S.; LIMA, J. F.; CARVALHO, G. C.; RAMOS, Y. A. L.; PEREIRA, N. Z.; VIEIRA, N. P.; ZANIBONI, M. C.; SATO, M. N.; AOKI, V.
  • article 19 Citação(ões) na Scopus
    The dysfunctional innate immune response triggered by Toll-like receptor activation is restored by TLR7/TLR8 and TLR9 ligands in cutaneous lichen planus
    (2015) DOMINGUES, R.; CARVALHO, G. Costa de; OLIVEIRA, L. M. da Silva; TANIGUCHI, E. Futata; ZIMBRES, J. M.; AOKI, V.; DUARTE, A. J. da Silva; SATO, M. N.
    BackgroundLichen planus (LP) is a chronic inflammatory mucocutaneous disease. Toll-like receptors (TLRs) bind numerous exogenous and endogenous antigens by recognizing conserved pathogen-associated molecular patterns (PAMPs) and have the ability to induce the production of proinflammatory cytokines. Therefore, alterations in innate immunity could explain the inflammation and T-cell autoreactivity leading to the development of LP disease. ObjectivesTo evaluate how the host innate immune response to PAMPs is affected by cutaneous LP, primarily by using TLR agonists to induce proinflammatory cytokine secretion from peripheral blood mononuclear cells (PBMCs). MethodsPBMCs from patients with LP and healthy control (HC) individuals were stimulated with agonists of TLR2/TLR1 (pam3csk4), TLR3 [poly(I:C)-RIG], TLR4 (lipopolysaccharide), TLR5 (flagellin), TLR7 (imiquimod), TLR7/TLR8 (CL097) and TLR9 (CpG). Cytokines from culture supernatants (n=10-12) andserum chemokines and cytokines (n=22-24) were measured using flow cytometry. ResultsActivation through the TLR2, TLR4 and TLR5 pathways induced increased tumour necrosis factor (TNF)- secretion by PBMCs from individuals with LP compared with the HC group. In contrast, activation through TLR3 and TLR7 was impaired in the LP group, leading to decreased TNF- secretion. Moreover, intracellular TLR activation resulted in reduced interleukin (IL)-1 and IL-6 secretion. Notably, individuals with LP became responders on stimulation with TLR7/TLR8 and TLR9 agonists; responses were measured as increases in interferon (IFN)- production. Detectable TNF- and high CXCL9 and CXCL10 serum levels were observed in patients with LP, suggesting their potential use as markers of the inflammatory status in LP. ConclusionsThese findings point to a defect in the TLR signalling pathways in cutaneous LP. Agonists of TLR7/TLR8 or TLR9 overcame impaired IFN- secretion in LP, strategically acting as adjuvants to improve the type I response.
  • article 14 Citação(ões) na Scopus
    Upregulation of Innate Antiviral Restricting Factor Expression in the Cord Blood and Decidual Tissue of HIV-Infected Mothers
    (2013) PEREIRA, Natalli Zanete; CARDOSO, Elaine Cristina; OLIVEIRA, Luanda Mara da Silva; LIMA, Josenilson Feitosa de; BRANCO, Anna Claudia Calvielli Castelo; RUOCCO, Rosa Maria de Souza Aveiro; ZUGAIB, Marcelo; OLIVEIRA FILHO, Joao Bosco de; DUARTE, Alberto Jose da Silva; SATO, Maria Notomi
    Programs for the prevention of mother-to-child transmission of HIV have reduced the transmission rate of perinatal HIV infection and have thereby increased the number of HIV-exposed uninfected (HEU) infants. Natural immunity to HIV-1 infection in both mothers and newborns needs to be further explored. In this study, we compared the expression of antiviral restricting factors in HIV-infected pregnant mothers treated with antiretroviral therapy (ART) in pregnancy (n=23) and in cord blood (CB) (n=16), placental tissues (n=10-13) and colostrum (n=5-6) samples and compared them to expression in samples from uninfected (UN) pregnant mothers (n=21). Mononuclear cells (MNCs) were prepared from maternal and CB samples following deliveries by cesarean section. Maternal (decidua) and fetal (chorionic villus) placental tissues were obtained, and colostrum was collected 24 h after delivery. The mRNA and protein expression levels of antiviral factors were then evaluated. We observed a significant increase in the mRNA expression levels of antiviral factors in MNCs from HIV-infected mothers and CB, including the apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5 alpha (TRIM-5 alpha), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-beta, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and alpha-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5 alpha protein levels in the villi and increased STING mRNA expression in both placental tissues were also observed in HIV-infected mothers compared with uninfected (UN) mothers. Additionally, colostrum cells from infected mothers showed increased tetherin and IFN-beta mRNA levels and CXCL9 protein levels. The data presented here indicate that antiviral restricting factor expression can be induced in utero in HIV-infected mothers. Future studies are warranted to determine whether this upregulation of antiviral factors during the perinatal period has a protective effect against HIV-1 infection.
  • article 3 Citação(ões) na Scopus
    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 Notomi
    Although 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.
  • article 14 Citação(ões) na Scopus
    Increased frequency of circulating Tc22/Th22 cells and polyfunctional CD38(-) T cells in HIV-exposed uninfected subjects
    (2015) OLIVEIRA, Luanda M. S.; LIMA, Josenilson F.; CERVANTES, Cesar A. C.; CASSEB, Jorge S.; MENDONCA, Marcelo; DUARTE, Alberto J. S.; SATO, Maria N.
    Some individuals are resistant to HIV-1 infection despite repeated exposure to the virus, suggesting the presence of a complex antiviral response. Innate factors like IL-22 exert gut mucosal protection and polyfunctional T cells have been associated with low progression in HIV infection; therefore, we evaluated the frequencies of CD4+ and CD8+ T cell-secreting cytokines, including Tc22/Th22 cells and polyfunctional T cells in HIV-1-exposed uninfected individuals (EUs), their HIV-1-infected partners and healthy controls. EUs exhibited an increased frequency of p15 Gag CD4+ IL-22+ secreting T cells, whereas HIV-infected partners demonstrated a high frequency of CD4+ IL-17+ T cells in response to p24. Similar responses of Th22 and Tc22 cells to Gag peptides and Staphylococcal enterotoxin B (SEB) stimulation were detected in the serodiscordant couples. However, polyfunctionality in HIV subjects was associated with an HIV Gag response of CD38+ T cells, whereas polyfunctionality for EUs was induced upon SEB stimulation by CD38-T cells. EUs demonstrated the presence of Tc22/Th22 cells and polyfunctional CD38-T cells with a low activation profile. These data suggest that SEB-induced polyfunctional CD4+ and CD8+ T cells together with Tc22/Th22 cells in EU individuals can provide an immunological advantage in the response to pathogens such as HIV-1.