NATALLI ZANETE PEREIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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- 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.
- 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.
- 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.
- Polyfunctional natural killer cells with a low activation profile in response to Toll-like receptor 3 activation in HIV-1-exposed seronegative subjects(2017) LIMA, Josenilson F.; OLIVEIRA, Luanda M. S.; PEREIRA, Natalli Z.; DUARTE, Alberto J. S.; SATO, Maria N.Natural killer (NK) cells are the main mediator of the cytotoxic response in innate immunity and may be involved in resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Toll-like receptor (TLR) signalling is crucial for NK cell activation. Here, we investigated the polyfunctional NK cell response to TLR3 activation in serodiscordant couples. ESN subjects showed increased IFN-gamma. and CD107a expression in both NK subsets, CD56(bright) and CD56(dim) cells, in response to stimulation with a TLR3 agonist, while expression was impaired in the HIV-1-infected partners. TLR3-induced expression of IFN-gamma, TNF and CD107a by polyfunctional CD56bright NK cells was more pronounced in ESN individuals than that in healthy controls. Activated NK cells, as determined by CD38 expression, were increased only in the HIV-1-infected partners, with reduced IFN-gamma. and CD107a expression. Moreover, CD38(+) NK cells of the HIV-1-infected partners were associated with increased expression of inhibitory molecules, such as NKG2A, PD- 1 and Tim-3, while NK cells from ESN subjects showed decreased NKG2A expression. Altogether, these findings indicate that NK cells of ESN individuals were highly responsive to TLR3 activation and had a polyfunctional NK cell phenotype, while the impaired TLR3 response in HIV-1-infected partners was associated with an inhibitory/ exhaustion NK cell phenotype.