NATALLI ZANETE PEREIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
12 resultados
Resultados de Busca
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- 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.
- 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.
- COVID-19 Disease Course in Former Smokers, Smokers and COPD Patients(2021) ALBERCA, Ricardo Wesley; LIMA, Julia Cataldo; OLIVEIRA, Emily Araujo de; GOZZI-SILVA, Sarah Cristina; RAMOS, Yasmim Alefe Leuzzi; ANDRADE, Milena Mary de Souza; BESERRA, Danielle Rosa; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; PIETROBON, Anna Julia; PEREIRA, Natalli Zanete; TEIXEIRA, Franciane Mouradian Emidio; FERNANDES, Iara Grigoletto; DUARTE, Alberto Jose da Silva; BENARD, Gil; SATO, Maria NotomiThe severe respiratory and systemic disease named coronavirus disease-2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, the COVID-19 pandemic presents a huge social and health challenge worldwide. Many different risk factors are associated with disease severity, such as systemic arterial hypertension, diabetes mellitus, obesity, older age, and other co-infections. Other respiratory diseases such as chronic obstructive pulmonary disease (COPD) and smoking are common comorbidities worldwide. Previous investigations have identified among COVID-19 patients smokers and COPD patients, but recent investigations have questioned the higher risk among these populations. Nevertheless, previous reports failed to isolate smokers and COPD patients without other comorbidities. We performed a longitudinal evaluation of the disease course of smokers, former smokers, and COPD patients with COVID-19 without other comorbidities, from hospitalization to hospital discharge. Although no difference between groups was observed during hospital admission, smokers and COPD patients presented an increase in COVID-19-associated inflammatory markers during the disease course in comparison to non-smokers and former smokers. Our results demonstrated that smoking and COPD are risk factors for severe COVID-19 with possible implications for the ongoing pandemic.
- SARS-CoV-2 Infection and CMV Dissemination in Transplant Recipients as a Treatment for Chagas Cardiomyopathy: A Case Report(2021) GOZZI-SILVA, Sarah Cristina; BENARD, Gil; ALBERCA, Ricardo Wesley; YENDO, Tatiana Mina; TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; BESERRA, Danielle Rosa; PIETROBON, Anna Julia; OLIVEIRA, Emily Araujo de; BRANCO, Anna Claudia Calvielli Castelo; ANDRADE, Milena Mary de Souza; FERNANDES, Iara Grigoletto; PEREIRA, Natalli Zanete; RAMOS, Yasmim Alefe Leuzzi; LIMA, Julia Cataldo; PROVENCI, Bruna; MANGINI, Sandrigo; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has infected over 90 million people worldwide, therefore it is considered a pandemic. SARS-CoV-2 infection can lead to severe pneumonia, acute respiratory distress syndrome (ARDS), septic shock, and/or organ failure. Individuals receiving a heart transplantation (HT) may be at higher risk of adverse outcomes attributable to COVID-19 due to immunosuppressives, as well as concomitant infections that may also influence the prognoses. Herein, we describe the first report of two cases of HT recipients with concomitant infections by SARS-CoV-2, Trypanosoma cruzi, and cytomegalovirus (CMV) dissemination, from the first day of hospitalization due to COVID-19 in the intensive care unit (ICU) until the death of the patients.
- Platelet-Based Biomarkers for Diagnosis and Prognosis in COVID-19 Patients(2021) ALBERCA, Ricardo Wesley; SOLIS-CASTRO, Rosa Liliana; SOLIS-CASTRO, Maria Edith; CARDOSO, Fernanda; DUARTE, Alberto Jose da Silva; OLIVEIRA, Luana de Mendonca; PEREIRA, Natalli Zanete; GOZZI-SILVA, Sarah Cristina; OLIVEIRA, Emily Araujo de; AOKI, Valeria; ORFALI, Raquel Leao; BESERRA, Danielle Rosa; ANDRADE, Milena Mary de Souza; SATO, Maria NotomiCoronavirus disease 2019 (COVID-19) caused millions of deaths worldwide. COVID-19's clinical manifestations range from no symptoms to a severe acute respiratory syndrome, which can result in multiple organ failure, sepsis, and death. Severe COVID-19 patients develop pulmonary and extrapulmonary infections, with a hypercoagulable state. Several inflammatory or coagulatory biomarkers are currently used with predictive values for COVID-19 severity and prognosis. In this manuscript, we investigate if a combination of coagulatory and inflammatory biomarkers could provide a better biomarker with predictive value for COVID-19 patients, being able to distinguish between patients that would develop a moderate or severe COVID-19 and predict the disease outcome. We investigated 306 patients with COVID-19, confirmed by severe acute respiratory syndrome coronavirus 2 RNA detected in the nasopharyngeal swab, and retrospectively analyzed the laboratory data from the first day of hospitalization. In our cohort, biomarkers such as neutrophil count and neutrophil-to-lymphocyte ratio from the day of hospitalization could predict if the patient would need to be transferred to the intensive care unit but failed to identify the patients & PRIME; outcomes. The ratio between platelets and inflammatory markers such as creatinine, C-reactive protein, and urea levels is associated with patient outcomes. Finally, the platelet/neutrophil-to-lymphocyte ratio on the first day of hospitalization can be used with predictive value as a novel severity and lethality biomarker in COVID-19. These new biomarkers with predictive value could be used routinely to stratify the risk in COVID-19 patients since the first day of hospitalization.
- 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.
- Frequencies of CD33+CD11b+HLA-DR-CD14-CD66b+and CD33+CD11b+HLA-DR-CD14+CD66b-Cells in Peripheral Blood as Severity Immune Biomarkers in COVID-19(2020) ALBERCA, Ricardo Wesley; ANDRADE, Milena Mary de Souza; BRANCO, Anna Claudia Calvielli Castelo; PIETROBON, Anna Julia; PEREIRA, Natalli Zanete; FERNANDES, Iara Grigoletto; OLIVEIRA, Luana de Mendonca; TEIXEIRA, Franciane Mouradian Emidio; BESERRA, Danielle Rosa; OLIVEIRA, Emily Araujo de; GOZZI-SILVA, Sarah Cristina; RAMOS, Yasmim Alefe Leuzzi; BRITO, Cyro Alves de; ARNONE, Marcelo; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCommon clinical features of patients with Coronavirus disease-2019 (COVID-19) vary from fever, to acute severe respiratory distress syndrome. Several laboratory parameters are reported as indicators of COVID-19 severity. We hereby describe the possible novel severity biomarkers for COVID-19, CD11b+CD33+HLA-DR-CD14+ cells and CD11b+CD33+HLA-DR-CD66b+ cells.
- 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.
- Staphylococcus aureus enterotoxins modulate IL-22-secreting cells in adults with atopic dermatitis(2018) ORFALI, Raquel Leao; OLIVEIRA, Luanda Mara da Silva; LIMA, Josenilson Feitosa de; CARVALHO, Gabriel Costa de; RAMOS, Yasmim Alefe Leuzzi; PEREIRA, Natalli Zanete; PEREIRA, Naiura Vieira; ZANIBONI, Mariana Colombini; SOTTO, Mirian Nacagami; DUARTE, Alberto Jose da Silva; SATO, Maria Notomi; AOKI, ValeriaAtopic dermatitis (AD) is a chronic inflammatory immune-mediated skin disease characterized by skin colonization by Staphylococcus aureus. Interleukin (IL)-22, in cooperation with IL-17, triggers antimicrobial peptide elaboration and enhances certain immunological responses. In AD, IL-22 is related to epidermal hyperplasia, keratinocyte apoptosis, and inhibition of antimicrobial peptide (AMP) production. We aimed to evaluate the impact of staphylococcal enterotoxins on the Tc22/Th22 induction in the peripheral blood of AD patients and on CD4(+/)CD8(+)T cells expressing IL-22 in AD skin. Our study showed inhibition of the staphylococcal enterotoxins A and B (SEA and SEB) response by Th22 (CD4(+)IL22(+)IL-17A(-)IFN-gamma(-)) cells in AD patients. In contrast, Tc22 (CD8(+)IL-22(+)IL-17A(-)IFN-gamma(-)) cells were less susceptible to the inhibitory effects of staphylococcal enterotoxins and exhibited an enhanced response to the bacterial stimuli. In AD skin, we detected increased IL-22 transcript expression and T lymphocytes expressing IL-22. Together, our results provide two major findings in response to staphylococcal enterotoxins in adults with AD: dysfunctional CD4(+)IL-22 secreting T cells and increased Tc22 cells. Our hypothesis reinforces the relevance of CD8 T cells modulated by staphylococcal enterotoxins as a potential source of IL-22 in adults with AD, which is relevant for the maintenance of immunological imbalance.