NATALIA BARROS CERQUEIRA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
8 resultados
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conferenceObject Attitudes and Knowledge About HIV PrEP Among Infectious Diseases Physicians in Brazil(2018) CERQUEIRA, Natalia; VASCONCELOS, Ricardo; HOJILLA, Carlo; KALLAS, Esper; AVELINO-SILVA, Vivian- MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection(2018) PAQUIN-PROULX, Dominic; AVELINO-SILVA, Vivian I.; SANTOS, Bianca A. N.; BARSOTTI, Nathalia Silveira; SIROMA, Fabiana; RAMOS, Jessica Fernandes; TONACIO, Adriana Coracini; SONG, Alice; MAESTRI, Alvino; CERQUEIRA, Natalia Barros; FELIX, Alvina Clara; LEVI, Jose Eduardo; GREENSPUN, Benjamin C.; ROUGVIE, Miguel de Mulder; ROSENBERG, Michael G.; NIXON, Douglas F.; KALLAS, Esper G.Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are pre-dominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barre A syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFN gamma response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFN gamma in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.
- Latent Mycobacterium tuberculosis Infection Is Associated With a Higher Frequency of Mucosal-Associated Invariant T and Invariant Natural Killer T Cells.(2018) PAQUIN-PROULX, Dominic; COSTA, Priscilla R.; SILVEIRA, Cassia G. Terrassani; MARMORATO, Mariana P.; CERQUEIRA, Natalia B.; SUTTON, Matthew S.; O'CONNOR, Shelby L.; CARVALHO, Karina I.; NIXON, Douglas F.; KALLAS, Esper G.Increasing drug resistance and the lack of an effective vaccine are the main factors contributing to Mycobacterium tuberculosis (Mtb) being a major cause of death globally. Despite intensive research efforts, it is not well understood why some individuals control Mtb infection and some others develop active disease. HIV-1 infection is associated with an increased incidence of active tuberculosis, even in virally suppressed individuals. Mucosal-associated invariant T (MAIT) and invariant natural killer T (iNKT) cells are innate T cells that can recognize Mtb-infected cells. Contradicting results regarding the frequency of MAIT cells in latent Mtb infection have been reported. In this confirmatory study, we investigated the frequency, phenotype, and IFN gamma production of MAIT and iNKT cells in subjects with latent or active Mtb infection. We found that the frequency of both cell types was increased in subjects with latent Mtb infection compared with uninfected individuals or subjects with active infection. We found no change in the expression of HLA-DR, PD-1, and CCR6, as well as the production of IFN. by MAIT and iNKT cells, among subjects with latent Mtb infection or uninfected controls. The proportion of CD4-CD8+ MAIT cells in individuals with latent Mtb infection was, however, increased. HIV-1 infection was associated with a loss of MAIT and iNKT cells, and the residual cells had elevated expression of the exhaustion marker PD-1. Altogether, the results suggest a role for MAIT and iNKT cells in immunity against Mtb and show a deleterious impact of HIV-1 infection on those cells.
- Syndemics among individuals enrolled in the PrEP Brasil Study(2018) BONI, Raquel B. De; MACHADO, Iona K.; VASCONCELLOS, Mauricio T. L. De; HOAGLAND, Brenda; KALLAS, Esper G.; MADRUGA, Jose Valdez; FERNANDES, Nilo M.; CERQUEIRA, Natalia B.; MOREIRA, Ronaldo I.; GOULART, Silvia P.; VELOSO, Valdilea G.; GRINSZTEJN, Beatriz; LUZ, Paula M.Background: Concurrent psychosocial problems may synergistically increase the risk of HIV infection (syndemics), representing a challenge for prevention. We aimed to evaluate the prevalence and associated factors of syndemics among men who have sex with men (MSM) and transgender women (TGW) enrolled in the Brazilian pre-exposure prophylaxis demonstration study (PrEP Brasil Study). Methods: Secondary cross-sectional analysis of the PrEP Brasil Study was performed. Of 450 HIV-seronegative MSM/TGW enrolled in the PrEP Brasil Study- conducted at Rio de Janeiro and Sao Paulo, Brazil- 421 participants with complete data were included in the present analysis. Syndemics was defined as occurrence of 2 of the following conditions: polysubstance (2) use, binge drinking, positive depression screen, compulsive sexual behavior, and intimate partner violence (IPV). Results: The prevalence of recent polysubstance use was 22.8%, binge drinking 51.1%, positive depression screening 5.2%, compulsive sexual behavior 7.1%, and IPV 7.3%. Syndemics prevalence was 24.2%, and associated factors were younger age (adjusted Odds Ratio (aOR) 0.95, 95% Confidence Interval (95% CI) 0.92-0.98 per year increase), TGW vs. MSM (aOR 3.09, 95% CI: 1.2-8.0), some college education or more vs. less than college (aOR 2.49, 95% CI: 1.31-4.75), and multiple male sexual partners in prior 3 months (aOR 1.69, 95% CI: 0.92-3.14). Conclusion: Given the high prevalence of syndemics, particularly of polysubstance use and binge drinking, PrEP delivery offers an opportunity to diagnose and intervene in mental and social well-being.
- HLA-C DOWNREGULATION BY HIV ADAPTS TO HOST HLA GENOTYPE(2018) APPS, Richard; BACHTEL, Nathaniel; UMVILIGIHOZO, Gisele; PICKERING, Suzanne; MOTA, Talia; LIANG, Hua; PRETE, Gregory Del; CHATTERJEE, Pramita; LEE, Guinevere; THOMAS, Rasmi; BROCKMAN, Mark; NEIL, Stuart; CARRINGTON, Mary; BWANA, Bosco; BANGSBERG, David; MARTIN, Jeffrey; KALLAS, Esper; DONINI, Camila; CERQUEIRA, Natalia; O'DOHERTY, Una; HAHN, Beatrice; JONES, Brad; BRUMME, Zabrina; NIXON, Douglas
conferenceObject TOLL-LIKE RECEPTOR SIGNALING PATHWAY IS DIFFERENTIALLY MODULATED IN PATIENTS WITH DENGUE WITHOUT WARNING SIGNS AND DENGUE WITH WARNING SIGNS(2018) BRUNIALTI, Milena K. C.; CERQUEIRA, Natalia; MAESTRI, Alvino; CHAVES, Lucas; LEVI, Jose E.; PANNUTI, Claudio S.; KALLAS, Esper G.; BURATTINI, Marcelo N.; SALOMAO, ReinaldoconferenceObject Retention and Persistance on PrEP for MSM and TGW: 96-week Results of the PrEP Brazil Demonstration Study(2018) VELOSO, Valdilea G.; TORRES, Thiago Silva; MOREIRA, Ronaldo I.; LEITE, Iuri C.; KALLAS, Esper G.; CERQUEIRA, Natalia B.; MADRUGA, Jose V.; GOULART, Silvia P.; FERNANDES, Nilo M.; SANTOS, Tony A.; FREITAS, Josias S.; MONTEIRO, Laylla; LACERDA, Marcus V.; ALENCASTRO, Paulo; MARINS, Luana M. S.; NAZER, Sandro; CARDOSO, Sandra Wagner; LUZ, Paula Mendes; HOAGLAND, Brenda; GRINSZTEJN, Beatriz- HLA-C downregulation by HIV-1 adapts to host HLA genotype(2018) BECHTEL, Nathaniel D.; UMVILIGIHOZO, Gisele; PICKERING, Suzanne; MOTA, Talia M.; LIANG, Hua; PRETE, Gregory Q. Del; CHATTERJEE, Pramita; LEE, Guinevere Q.; THOMAS, Rasmi; BROCKMAN, Mark A.; NEIL, Stuart; CARRINGTON, Mary; BWANA, Bosco; BANGSBERG, David R.; MARTIN, Jeffrey N.; KALLAS, Esper G.; DONINI, Camila S.; CERQUEIRA, Natalia B.; O'DOHERTY, Una T.; HAHN, Beatrice H.; JONES, R. Brad; BRUMME, Zabrina L.; NIXON, Douglas F.; APPS, RichardHIV-1 can downregulate HLA-C on infected cells, using the viral protein Vpu, and the magnitude of this downregulation varies widely between primary HIV-1 variants. The selection pressures that result in viral downregulation of HLA-C in some individuals, but preservation of surface HLA-C in others are not clear. To better understand viral immune evasion targeting HLA-C, we have characterized HLA-C downregulation by a range of primary HIV-1 viruses. 128 replication competent viral isolates from 19 individuals with effective anti-retroviral therapy, show that a substantial minority of individuals harbor latent reservoir virus which strongly downregulates HLA-C. Untreated infections display no change in HLA-C downregulation during the first 6 months of infection, but variation between viral quasispecies can be detected in chronic infection. Vpu molecules cloned from plasma of 195 treatment naive individuals in chronic infection demonstrate that downregulation of HLA-C adapts to host HLA genotype. HLA-C alleles differ in the pressure they exert for downregulation, and individuals with higher levels of HLA-C expression favor greater viral downregulation of HLA-C. Studies of primary and mutant molecules identify 5 residues in the transmembrane region of Vpu, and 4 residues in the transmembrane domain of HLA-C, which determine interactions between Vpu and HLA. The observed adaptation of Vpu-mediated downregulation to host genotype indicates that HLA-C alleles differ in likelihood of mediating a CTL response that is subverted by viral downregulation, and that preservation of HLA-C expression is favored in the absence of these responses. Finding that latent reservoir viruses can downregulate HLA-C could have implications for HIV-1 cure therapy approaches in some individuals.