FERNANDA ROMANO BRUNO
Índice h a partir de 2011
5
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- HCV Viremia Drives an Increment of CD86 Expression by Myeloid Dendritic Cells(2013) MALTA, F. M.; BRUNO, F. R.; CARVALHO, K. I.; NASTRI, A. C. S. S.; KALIL, J.; CARRILHO, F. J.; KALLAS, E. G.; PINHO, J. R. R.The host immune response, including innate and adaptive immunity, plays a critical role in determining the outcome of viral infection. Nevertheless, little is known about the exact reasons for the failure of the host immune system in controlling hepatitis C virus (HCV) infection. Impairment of dendritic cells (DCs) function is probably one of the mechanisms responsible for immune evasion of HCV. In this study, the frequency and phenotype of DCs subsets were analyzed in three groups: HCV-infected individuals who developed viral persistence (1), HCV-infected individuals who spontaneously cleared the virus (2) and HCV-seronegative uninfected subjects (3). The results showed that the frequency of DCs subsets was not statistically significant between groups. Plasmacytoid DCs circulating exhibited an immature phenotype characterized by low expression of CD86. On the other hand, CD86 expression in myeloid DCs was significantly higher in chronic infected individuals compared to healthy controls (P=0.037). A positive correlation was observed between CD86(+) myeloid DC (mDC) and HCV viral load (r=0.4121, P=0.0263). These results suggest that HCV did not have an inhibitory effect on mDC maturation and the HCV viremia drives the increase of CD86 expression in mDC. The regulation of DCs maturation and migration lies at the level of intracellular signaling. HCV can activate or block intracellular signaling pathways and alter DC function. In conclusion, the present study suggests that imbalance of DC maturation by the virus represents a mechanism of evasion of the immune system despite the fact that HCV viremia appears to exert a stimulatory effect on cell-surface immune phenotype. J Med. Virol. 85:1919-1924, 2013. (c) 2013 Wiley Periodicals, Inc.
- Recurrence of COVID-19 associated with reduced T-cell responses in a monozygotic twin pair(2022) V, Mateus de Castro; SANTOS, Keity S.; APOSTOLICO, Juliana S.; FERNANDES, Edgar R.; ALMEIDA, Rafael R.; LEVIN, Gabriel; MAGAWA, Jhosiene Y.; NUNES, Joao Paulo S.; BRUNI, Mirian; YAMAMOTO, Marcio M.; LIMA, Ariane C.; SILVA, Monize V. R.; MATOS, Larissa R. B.; CORIA, Vivian R.; CASTELLI, Erick C.; SCLIAR, Marilia O.; KURAMOTO, Andreia; BRUNO, Fernanda R.; JACINTHO, Lucas C.; NUNES, Kelly; WANG, Jaqueline Y. T.; COELHO, Veronica P.; NETO, Miguel Mitne; MACIEL, Rui M. B.; NASLAVSKY, Michel S.; PASSOS-BUENO, Maria Rita; BOSCARDIN, Silvia B.; ROSA, Daniela S.; KALIL, Jorge; ZATZ, Mayana; CUNHA-NETO, EdecioRecurrence of COVID-19 in recovered patients has been increasingly reported. However, the immune mechanisms behind the recurrence have not been thoroughly investigated. The presence of neutralizing antibodies (nAbs) in recurrence/reinfection cases suggests that other types of immune response are involved in protection against recurrence. Here, we investigated the innate type I/III interferon (IFN) response, binding and nAb assays and T-cell responses to severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) with IFN gamma (IFN gamma) enzyme-linked spot assay (ELISPOT) in three pairs of young adult monozygotic (MZ) twins with previous confirmed COVID-19, one of them presenting a severe recurrence four months after the initial infection. Twin studies have been of paramount importance to comprehend the immunogenetics of infectious diseases. Each MZ twin pair was previously exposed to SARS-CoV-2, as seen by clinical reports. The six individuals presented similar overall recovered immune responses except for the recurrence case, who presented a drastically reduced number of recognized SARS-CoV-2 T-cell epitopes on ELISPOT as compared to her twin sister and the other twin pairs. Our results suggest that the lack of a broad T-cell response to initial infection may have led to recurrence, emphasizing that an effective SARS-CoV-2-specific T-cell immune response is key for complete viral control and avoidance of clinical recurrence of COVID-19.
- HTLV-1 Tax Specific CD8+ T Cells Express Low Levels of Tim-3 in HTLV-1 Infection: Implications for Progression to Neurological Complications(2011) NDHLOVU, Lishomwa C.; LEAL, Fabio E.; HASENKRUG, Aaron M.; JHA, Aashish R.; CARVALHO, Karina I.; ECCLES-JAMES, Ijeoma G.; BRUNO, Fernanda R.; VIEIRA, Raphaella G. S.; YORK, Vanessa A.; CHEW, Glen M.; JONES, R. Brad; TANAKA, Yuetsu; NETO, Walter K.; SANABANI, Sabri S.; OSTROWSKI, Mario A.; SEGURADO, Aluisio C.; NIXON, Douglas F.; KALLAS, Esper G.The T cell immunoglobulin mucin 3 (Tim-3) receptor is highly expressed on HIV-1-specific T cells, rendering them partially ""exhausted'' and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis), we investigated the expression of the Tim-3 receptor on CD8(+) T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8(+) and CD4(+) T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8(+) T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3(+) and Tim-3(-) fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications.
- Reduced T Cell and Antibody Responses to Inactivated Coronavirus Vaccine Among Individuals Above 55 Years Old(2022) MEDEIROS, Giuliana X.; SASAHARA, Greyce Luri; MAGAWA, Jhosiene Y.; NUNES, Joao Paulo S.; BRUNO, Fernanda R.; KURAMOTO, Andreia C.; ALMEIDA, Rafael R.; FERREIRA, Marcelo A.; SCAGION, Guilherme P.; CANDIDO, Erika D.; LEAL, Fabyano B.; OLIVEIRA, Danielle B. L.; DURIGON, Edison L.; SILVA JR., Roberto Carlos V.; ROSA, Daniela S.; BOSCARDIN, Silvia B.; COELHO, Veronica; KALIL, Jorge; SANTOS, Keity S.; CUNHA-NETO, EdecioCoronaVac is an inactivated SARS-CoV-2 vaccine that has been rolled out in several low and middle-income countries including Brazil, where it was the mainstay of the first wave of immunization of healthcare workers and the elderly population. We aimed to assess the T cell and antibody responses of vaccinated individuals as compared to convalescent patients. We detected IgG against SARS-CoV-2 antigens, neutralizing antibodies against the reference Wuhan SARS-CoV-2 strain and used SARS-CoV-2 peptides to detect IFN-g and IL-2 specific T cell responses in a group of CoronaVac vaccinated individuals (N = 101) and convalescent (N = 72) individuals. The frequency among vaccinated individuals, of whom 96% displayed T cell and/or antibody responses to SARS-CoV-2, is comparable to 98.5% responses of convalescent individuals. We observed that among vaccinated individuals, men and individuals 55 years or older developed significantly lower anti-RBD, anti-NP and neutralization titers against the Wuhan strain and antigen-induced IL-2 production by T cells. Neutralizing antibody responses for Gamma variant were even lower than for the Wuhan strain. Even though some studies indicated CoronaVac helped reduce mortality among elderly people, considering the appearance of novel variants of concern, CoronaVac vaccinated individuals above 55 years old are likely to benefit from a heterologous third dose/booster vaccine to increase immune response and likely protection.
- Expansion in CD39(+) CD4(+) Immunoregulatory T Cells and Rarity of Th17 Cells in HTLV-1 Infected Patients Is Associated with Neurological Complications(2013) LEAL, Fabio E.; NDHLOVU, Lishomwa C.; HASENKRUG, Aaron M.; BRUNO, Fernanda R.; CARVALHO, Karina I.; WYNN-WILLIAMS, Harry; NETO, Walter K.; SANABANI, Sabri S.; SEGURADO, Aluisio C.; NIXON, Douglas F.; KALLAS, Esper G.HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develops HAM/TSP. CD4(+) T cells are the main target of infection and play a pivotal role in regulating immunity to HTLV and are hypothesized to participate in the pathogenesis of HAM/TSP. The CD39 ectonucleotidase receptor is expressed on CD4(+) T cells and based on co-expression with CD25, marks T cells with distinct regulatory (CD39(+)CD25(+)) and effector (CD39(+)CD25(-)) function. Here, we investigated the expression of CD39 on CD4(+) T cells from a cohort of HAM/TSP patients, HTLV-1 asymptomatic carriers (AC), and matched uninfected controls. The frequency of CD39(+)CD4(+) T cells was increased in HTLV-1 infected patients, regardless of clinical status. More importantly, the proportion of the immunostimulatory CD39(+)CD25(-) CD4+ T-cell subset was significantly elevated in HAM/TSP patients as compared to AC and phenotypically had lower levels of the immunoinhibitory receptor, PD-1. We saw no difference in the frequency of CD39(+)CD25(+) regulatory (Treg) cells between AC and HAM/TSP patients. However, these cells transition from being anergic to displaying a polyfunctional cytokine response following HTLV-1 infection. CD39(-)CD25(+) T cell subsets predominantly secreted the inflammatory cytokine IL-17. We found that HAM/TSP patients had significantly fewer numbers of IL-17 secreting CD4(+) T cells compared to uninfected controls. Taken together, we show that the expression of CD39 is upregulated on CD4(+) T cells HAM/TSP patients. This upregulation may play a role in the development of the proinflammatory milieu through pathways both distinct and separate among the different CD39 T cell subsets. CD39 upregulation may therefore serve as a surrogate diagnostic marker of progression and could potentially be a target for interventions to reduce the development of HAM/TSP.