NATALLI ZANETE PEREIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
20 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 20
- Profile of differentially expressed Toll-like receptor signaling genes in the natural killer cells of patients with Sezary syndrome(2017) MANFRERE, Kelly C. G.; TORREALBA, Marina P.; MIYASHIRO, Denis R.; PEREIRA, Natalli Z.; YOSHIKAWA, Fabio S. Y.; OLIVEIRA, Luana de M.; CURY-MARTINS, Jade; DUARTE, Alberto J. S.; SANCHES, Jose A.; SATO, Maria N.Sezary syndrome (SS), an aggressive and leukemic form of cutaneous T-cell lymphoma, usually results in shortened survival. Improving innate immunity in SS by targeting natural killer (NK) cells with Toll-like receptor (TLR) agonists could be an interesting modulatory strategy. We evaluated the NK cell populations in SS patients assessing activating and inhibitory receptors expression and profiled the differential expression of TLR signaling pathway genes in unstimulated NK cells and after TLR7/8 stimulation. We observed preserved CD56(bright) NK cells and a low percentage of CD56(dim) NK cells in the peripheral blood of SS patients compared to those in the healthy control group. Both NK cell populations showed down-modulation of NKG2C and NKG2D expression, which was associated with high serum levels of the soluble form of NKG2D ligands. In contrast, an expansion of ""memory"" CD57+ NKG2C+ NK cells and high cytomegalovirus antibody titers were detected in SS patients. Profiling of the TLR signaling genes in NK cells from SS patients showed an abundance of differentially expressed genes (DEGs) in NK cells in the unstimulated condition, with mostly up-regulation of NF kappa B/JNK p38 pathway genes, but there was down-regulation of type I (IFN-alpha/beta) and II (IFN-gamma) interferon and IL-12A. After activation of NK cells with TLR7/8 agonist, the down-regulated genes correlated with the IFN response, and IL-12 became up-regulated, together with other antitumor factors. NK cell activation with a dual agonist for TLR7 and TLR8 is able to induce the expression of IFN-gamma and type I IFN, which can improve immunity in SS patients.
- 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, ValeriaStaphylococcus 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.
- 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 NotomiZika 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.- 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.
- Obesity as a risk factor for COVID-19: an overview(2021) ALBERCA, Ricardo Wesley; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; PEREIRA, Natalli Zanete; SATO, Maria NotomiThe current coronavirus disease-2019 (COVID-19) pandemic presents a huge challenge for health-care systems worldwide. Many different risk factors are associated with disease severity, such as older age, diabetes, hypertension, and most recently obesity. The incidence of obesity has been on the rise for the past 25 years, reaching over 2 billion people throughout the world, and obesity itself could be considered a pandemic. In this review, we summarize aspects involved with obesity, such as changes in the immune response, nutritional factors, physiological factors, and the gut-lung axis, that impact the viral response and the COVID-19 prognosis.
- Pregnancy, Viral Infection, and COVID-19(2020) ALBERCA, Ricardo Wesley; PEREIRA, Natalli Zanete; OLIVEIRA, Luanda Mara Da Silva; GOZZI-SILVA, Sarah Cristina; SATO, Maria NotomiPregnancy comprises a unique immunological condition, to allow fetal development and to protect the host from pathogenic infections. Viral infections during pregnancy can disrupt immunological tolerance and may generate deleterious effects on the fetus. Despite these possible links between pregnancy and infection-induced morbidity, it is unclear how pregnancy interferes with maternal response to some viral pathogens. In this context, the novel coronavirus (SARS-CoV-2) can induce the coronavirus diseases-2019 (COVID-19) in pregnant women. The potential risk of vertical transmission is unclear, babies born from COVID-19-positive mothers seems to have no serious clinical symptoms, the possible mechanisms are discussed, which highlights that checking the children's outcome and more research is warranted. In this review, we investigate the reports concerning viral infections and COVID-19 during pregnancy, to establish a correlation and possible implications of COVID-19 during pregnancy and neonatal's health.
- 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
- Long-term effects of COVID-19 in diabetic and non-diabetic patients(2022) ALBERCA, Ricardo Wesley; RAMOS, Yasmim Alefe Leuzzi; PEREIRA, Natalli Zanete; BESERRA, Danielle Rosa; BRANCO, Anna Claudia Calvielli Castelo; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiThe literature presents several reports of the impact of glycemic control and diabetes in the inflammatory and coagulatory response during coronavirus disease 2019 (COVID-19). Nevertheless, the long-term impact of the COVID-19 in diabetic patients is still to be explored. Therefore, we recruited 128 patients and performed a longitudinal analysis on COVID-19-associated biomarkers of patients with COVID-19, tree and 6 months after COVID-19 recovery and put into perspective the possible long-term complication generated after COVID-19. In our investigation, we failed to verify any long-term modification on inflammatory biomarkers, but detected an increase in the glycemia and glycated hemoglobin in patients without any pre-existing history or diagnosis of diabetes (non-diabetic patients). Although diabetic and non-diabetic patients presented elevated levels of glycated hemoglobin, the c-peptide test indicated a normal beta cell function in all patients.
- 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.