NATALLI ZANETE PEREIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- 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.
- 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
- 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.
- IFN-gamma reshapes monocyte responsiveness in Sezary syndrome(2021) TORREALBA, Marina P.; MANFRERE, Kelly C. G.; YOSHIKAWA, Fabio S. Y.; PEREIRA, Natalli Z.; BRANCO, Anna C. C. C.; TEIXEIRA, Franciane M. E.; MIYASHIRO, Denis R.; MARTINS, Jade C.; DUARTE, Alberto J. S.; SANCHES, Jose A.; SATO, Maria N.
- Increased Expression on Innate Immune Factors in Placentas From HIV-Infected Mothers Concurs With Dampened Systemic Immune Activation(2020) PEREIRA, Natalli Zanete; BRANCO, Anna Claudia Calvielli Castelo; MANFRERE, Kelly Cristina Gomes; LIMA, Josenilson Feitosa de; YOSHIKAWA, Fabio Seiti Yamada; MILANEZ, Helaine Maria Besteti Pires Mayer; PEREIRA, Naiura Vieira; SOTTO, Miriam Nacagami; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiInnate immunity is one of the main protection mechanisms against viral infections, but how this system works at the maternal-fetal interface, especially during HIV infection, is still poorly known. In this study, we investigated the relationship between pregnancy and innate mechanisms associated with HIV immunity by evaluating the expression of DAMPs, inflammasome components and type I/III IFNs in placenta and serum samples from HIV-infected mothers and exposed newborns. Our results showed that most of these factors, including HMGB1, IL-1, and IFN, were increased in placental villi from HIV-infected mothers. Curiously, however, these factors were simultaneously repressed in serum from HIV-infected mothers and their exposed newborns, suggesting that pregnancy could restrict HIV immune activation systemically but preserve the immune response at the placental level. An effective local antiviral status associated with a suppressed inflammatory environment can balance the maternal immune response, promoting homeostasis for fetal development and protection against HIV infection in neonates.
- Antiviral Response Induced by Toll-Like Receptor (TLR) 7/TLR8 Activation Inhibits Human Immunodeficiency Virus Type 1 Infection in Cord Blood Macrophages(2022) PIETROBON, Anna J.; YOSHIKAWA, Fabio S. Y.; OLIVEIRA, Luana M.; PEREIRA, Natalli Z.; MATOZO, Tais; ALENCAR, Bruna C. de; DUARTE, Alberto J. S.; SATO, Maria N.Cord blood macrophages are more susceptible to HIV-1 infection. This vulnerability can be reversed under treatment with the type I interferon adjuvant CL097, which triggers inflammatory and antiviral responses in these cells, attenuating viral replication. Vertical transmission is the main mechanism of human immunodeficiency virus type 1 (HIV-1) infection in infants, who may develop high viremia and rapidly progress to AIDS. Innate immunity agonists can control HIV-1 replication in vitro, but the protective effect in the neonatal period remains unknown. Herein, we evaluated the immunomodulatory and antiviral effects of type I interferon (IFN-I) adjuvants on cord blood monocyte-derived macrophages upon HIV-1 infection. Despite the phenotypic and transcriptional similarities between cord blood and adult macrophages, cord blood cells were prone to viral replication when infected with HIV-1. However, treatment with CL097 efficiently promoted the antiviral and inflammatory responses and inhibited HIV-1 replication in cord blood cells in an NF-kappa B and autophagy activation-independent manner. Our data suggest that cord blood macrophages are able to establish antiviral responses induced by IFN-I adjuvants similar to those of their adult counterparts, revealing a potential adjuvant candidate to enhance the neonatal immune response.