PRISCILLA RAMOS COSTA

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LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina

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  • article 15 Citação(ões) na Scopus
    A generalizable method for estimating duration of HIV infections using clinical testing history and HIV test results
    (2019) PILCHER, Christopher D.; PORCO, Travis C.; FACENTE, Shelley N.; GREBE, Eduard; DELANEY, Kevin P.; MASCIOTRA, Silvina; KASSANJEE, Reshma; BUSCH, Michael P.; MURPHY, Gary; OWEN, S. Michele; WELTE, Alex; MATTEN, David; BRAND, Hilmarie; CHIBAWARA, Trust; MCKINNEY, Elaine; HALL, Jake; BUSCH, Michael; KEATING, Sheila; LEBEDEVA, Mila; HAMPTON, Dylan; PILCHER, Christopher; FACENTE, Shelley; MARSON, Kara; LAEYENDECKER, Oliver; QUINN, Thomas; BURNS, David; LITTLE, Susan; SANDS, Anita; HALLETT, Tim; OWEN, Sherry Michele; PAREKH, Bharat; SEXTON, Connie; PRICE, Matthew; KAMALI, Anatoli; LOEB, Lisa; MARTIN, Jeffrey; DEEKS, Steven G.; HOH, Rebecca; BARTOLOMEI, Zelinda; CERQUEIRA, Natalia; SANTOS, Breno; ZABTOSKI, Kellin; LIRA, Rita de Cassia Alves; SPERHACKE, Rosa Dea; MOTTA, Leonardo R.; PAGANELLA, Machline; KALLAS, Esper; TOMIYAMA, Helena; TOMIYAMA, Claudia; COSTA, Priscilla; NUNES, Maria A.; REIS, Gisele; SAUER, Mariana M.; NAKAGAWA, Zelinda; FERRARI, Lilian; AMARAL, Ana P.; MILANI, Karine; KARIM, Salim S. Abdool; KARIM, Quarraisha Abdool; NDUNGU, Thumbi; MAJOLA, Nelisile; SAMSUNDER, Natasha; NANICHE, Denise; MANDOMANDO, Inicio; V, Eusebio Macete; SANCHEZ, Jorge; LAMA, Javier; DUERR, Ann; CAPOBIANCHI, Maria R.; SULIGOI, Barbara; STRAMER, Susan; WILLIAMSON, Phillip; VERMEULEN, Marion; SABINO, Ester
    Objective: To determine the precision of new and established methods for estimating duration of HIV infection. Design: A retrospective analysis of HIV testing results from serial samples in commercially available panels, taking advantage of extensive testing previously conducted on 53 seroconverters. Methods: We initially investigated four methods for estimating infection timing: method 1, 'Fiebig stages' based on test results from a single specimen; method 2, an updated '4th gen' method similar to Fiebig stages but using antigen/antibody tests in place of the p24 antigen test; method 3, modeling of 'viral ramp-up' dynamics using quantitative HIV-1 viral load data from antibody-negative specimens; and method 4, using detailed clinical testing history to define a plausible interval and best estimate of infection time. We then investigated a 'two-step method' using data from both methods 3 and 4, allowing for test results to have come from specimens collected on different days. Results: Fiebig and '4th gen' staging method estimates of time since detectable viremia had similar and modest correlation with observed data. Correlation of estimates from both new methods (3 and 4), and from a combination of these two ('two-step method') was markedly improved and variability significantly reduced when compared with Fiebig estimates on the same specimens. Conclusion: The new 'two-step' method more accurately estimates timing of infection and is intended to be generalizable to more situations in clinical medicine, research, and surveillance than previous methods. An online tool is now available that enables researchers/clinicians to input data related to method 4, and generate estimated dates of detectable infection.
  • article 2 Citação(ões) na Scopus
    Plasmablast Expansion Following the Tetravalent, Live-Attenuated Dengue Vaccine Butantan-DV in DENV-Naive and DENV-Exposed Individuals in a Brazilian Cohort
    (2022) SILVEIRA, Cassia G. T.; MAGNANI, Diogo M.; COSTA, Priscilla R.; AVELINO-SILVA, Vivian I.; RICCIARDI, Michael J.; TIMENETSKY, Maria do Carmo S. T.; GOULART, Raphaella; CORREIA, Carolina A.; MARMORATO, Mariana P.; FERRARI, Lilian; NAKAGAWA, Zelinda B.; TOMIYAMA, Claudia; TOMIYAMA, Helena; KALIL, Jorge; PALACIOS, Ricardo; PRECIOSO, Alexander R.; WATKINS, David I.; KALLAS, Esper G.
    An effective vaccine against the dengue virus (DENV) should induce a balanced, long-lasting antibody (Ab) response against all four viral serotypes. The burst of plasmablasts in the peripheral blood after vaccination may reflect enriched vaccine-specific Ab secreting cells. Here we characterize the acute plasmablast responses from naive and DENV-exposed individuals following immunization with the live attenuated tetravalent (LAT) Butantan DENV vaccine (Butantan-DV). The frequency of circulating plasmablasts was determined by flow cytometric analysis of fresh whole blood specimens collected from 40 participants enrolled in the Phase II Butantan-DV clinical trial (NCT01696422) before and after (days 6, 12, 15 and 22) vaccination. We observed a peak in the number of circulating plasmablast at day 15 after vaccination in both the DENV naive and the DENV-exposed vaccinees. DENV-exposed vaccinees experienced a significantly higher plasmablast expansion. In the DENV-naive vaccinees, plasmablasts persisted for approximately three weeks longer than among DENV-exposed volunteers. Our findings indicate that the Butantan-DV can induce plasmablast responses in both DENV-naive and DENV-exposed individuals and demonstrate the influence of pre-existing DENV immunity on Butantan DV-induced B-cell responses.
  • article 1 Citação(ões) na Scopus
    Fetal-Maternal Hemorrhage in First-Trimester Intrauterine Hematoma
    (2021) NARCISO, Thaisa A. R. M.; HOSHIDA, Mara S.; COSTA, Priscilla R.; NIQUIRILO, Andrea; BIANCOLIN, Sckarlet E.; LIN, Lawrence H.; FRANCISCO, Rossana P. V.; BRIZOT, Maria L.
    Objective: The objective of this study was to compare the frequency and percentage of fetal hemoglobin (HbF%) by flow cytometry of (1) first-trimester asymptomatic patients with intrauterine hematoma (IUH), (2) first-trimester pregnant patients with vaginal bleeding (VB), and (3) first-trimester asymptomatic pregnant women without hematoma. Methods: Prospective study involving pregnant women in the first trimester of pregnancy. Patients with ultrasound findings of asymptomatic hematoma and with VB were paired with asymptomatic pregnant women of same gestational age without hematoma (control group [CG]). Maternal blood HbF% was evaluated by flow cytometry. The groups were compared in terms of circulating fetal hemoglobin and HbF%. Results: Sixty-six patients were selected, 22 with hematoma, 17 with bleeding, and 27 in the CG. Fetal hemoglobin was detected in 15 patients with hematoma (68.2%) and 13 with bleeding (76.5%) and in 20 of the control (74.1%) (p = 0.830). The mean HbF% of each group was 0.054, 0.012, and 0.042 for hematoma, bleeding, and control, respectively, and differences were not significant (p = 0.141). There was a moderate negative correlation between the volume of hematoma and HbF% (r(Spearman) = -0.527; p = 0.012). Conclusions: The fetal-maternal hemorrhage expressed by Hbf% in first-trimester pregnancies did not seem to differ between patients with and without ultrasound findings of IUH.
  • article 128 Citação(ões) na Scopus
    Prior Dengue Virus Exposure Shapes T Cell Immunity to Zika Virus in Humans
    (2017) GRIFONI, Alba; PHAM, John; SIDNEY, John; O'ROURKE, Patrick H.; PAUL, Sinu; PETERS, Bjoern; MARTINI, Sheridan R.; SILVA, Aruna D. de; RICCIARDI, Michael J.; MAGNANI, Diogo M.; SILVEIRA, Cassia G. T.; MAESTRI, Alvino; COSTA, Priscilla R.; DE-OLIVEIRA-PINTO, Luzia Maria; AZEREDO, Elzinandes Leal de; DAMASCO, Paulo Vieira; PHILLIPS, Elizabeth; MALLAL, Simon; SILVA, Aravinda M. de; COLLINS, Matthew; DURBIN, Anna; DIEHL, Sean A.; CERPAS, Cristhiam; BALMASEDA, Angel; KUAN, Guillermina; COLOMA, Josefina; HARRIS, Eva; CROWE JR., James E.; STONE, Mars; NORRIS, Phillip J.; BUSCH, Michael; VIVANCO-CID, Hector; COX, Josephine; GRAHAM, Barney S.; LEDGERWOOD, Julie E.; TURTLE, Lance; SOLOMON, Tom; KALLAS, Esper G.; WATKINS, David I.; WEISKOPF, Daniela; SETTE, Alessandro
    While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here, we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether preexisting dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with tetravalent dengue attenuated vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors but declines in DENV-preexposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells from DENV-preexposed donors selectively upregulated granzyme B and PD1, unlike DENV-naive donors. Finally, we discovered that ZIKV structural proteins (E, prM, and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins. IMPORTANCE The issue of potential ZIKV and DENV cross-reactivity and how preexisting DENV T cell immunity modulates Zika T cell responses is of great relevance, as the two viruses often cocirculate and Zika virus has been spreading in geographical regions where DENV is endemic or hyperendemic. Our data show that memory T cell responses elicited by prior infection with DENV recognize ZIKV-derived peptides and that DENV exposure prior to ZIKV infection influences the timing, magnitude, and quality of the T cell response. Additionally, we show that ZIKV-specific responses target different proteins than DENV-specific responses, pointing toward important implications for vaccine design against this global threat.
  • article 14 Citação(ões) na Scopus
    Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance
    (2019) SEMPA, Joseph B.; WELTE, Alex; BUSCH, Michael P.; HALL, Jake; HAMPTON, Dylan; FACENTE, Shelley N.; KEATING, Sheila M.; MARSON, Kara; PARKIN, Neil; PILCHER, Christopher D.; MURPHY, Gary; GREBE, Eduard; SEMP, Joseph; MATTEN, David; BRAND, Hilmarie; CHIBAWARA, Trust; MCKINNEY, Elaine; FACENTE, Shelley; KEATING, Sheila; LEBEDEVA, Mila; KASSANJEE, Reshma; LAEYENDECKER, Oliver; QUINN, Thomas; BURNS, David; LITTLE, Susan; SANDS, Anita; HALLETT, Tim; OWEN, Sherry Michele; PAREKH, Bharat; SEXTON, Connie; PRICE, Matthew; KAMALI, Anatoli; LOEB, Lisa; MARTIN, Jeffrey; DEEKS, Steven G.; HOH, Rebecca; BARTOLOMEI, Zelinda; CERQUEIRA, Natalia; SANTOS, Breno; ZABTOSKI, Kellin; LIRA, Rita de Cassia Alves; SPERHACKE, Rosa Dea; MOTTA, Leonardo R.; PAGANELLA, Machline; KALLAS, Esper; TOMIYAMA, Helena; TOMIYAMA, Claudia; COSTA, Priscilla; NUNES, Maria A.; REIS, Gisele; SAUER, Mariana M.; NAKAGAWA, Zelinda; FERRARI, Lilian; AMARAL, Ana P.; MILANI, Karine; KARIM, Salim S. Abdool; KARIM, Quarraisha Abdool; NDUNGU, Thumbi; MAJOLA, Nelisile; SAMSUNDER, Natasha; NANICHE, Denise; MANDOMANDO, Inacio; V, Eusebio Macete; SANCHEZ, Jorge; LAMA, Javier; DUERR, Ann; CAPOBIANCHI, Maria R.; SULIGOI, Barbara; STRAMER, Susan; WILLIAMSON, Phillip; VERMEULEN, Marion; SABINO, Ester
    Background Two manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply CDC-approved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg) for detecting 'recent' HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the two assays for incidence surveillance. Methods We ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens. We analysed concordance of assay results, assessed reproducibility using repeat testing and estimated mean durations of recent infection (MDRIs) and false-recent rates (FRRs) for a range of normalized optical density (ODn) thresholds, alone and in combination with viral load thresholds. We defined three hypothetical surveillance scenarios, similar to the Kenyan and South African epidemics, and a concentrated epidemic. These scenarios allowed us to evaluate the precision of incidence estimates obtained by means of various recent infection testing algorithms (RITAs) based on each of the two assays. Results The Maxim assay produced lower ODn values than the Sedia assay on average, largely as a result of higher calibrator readings (mean OD of 0.749 vs. 0.643), with correlation of normalized readings lower (R-2 = 0.908 vs. R-2 = 0.938). Reproducibility on blinded control specimens was slightly better for Maxim. The MDRI of a Maxim-based algorithm at the 'standard' threshold (ODn <= 1.5 & VL > 1,000) was 201 days (95% CI: 180,223) and for Sedia 171 (152,191). The difference Differences in MDRI were estimated at 32.7 (22.9,42.8) and 30.9 days (21.7,40.7) for the two algorithms, respectively. Commensurately, the Maxim algorithm had a higher FRR in treatment-naive subjects (1.7% vs. 1.1%). The two assays produced similar precision of incidence estimates in the three surveillance scenarios. Conclusions Differences between the assays can be primarily attributed to the calibrators supplied by the manufacturers. Performance for surveillance was extremely similar, although different thresholds were optimal (i.e. produced the lowest variance of incidence estimates) and at any given ODn threshold, different estimates of MDRI and FRR were obtained. The two assays cannot be treated as interchangeable: assay and algorithm-specific performance characteristic estimates must be used for survey planning and incidence estimation.
  • article 53 Citação(ões) na Scopus
    Global Assessment of Dengue Virus-Specific CD4(+) T Cell Responses in Dengue-Endemic Areas
    (2017) GRIFONI, Alba; ANGELO, Michael A.; LOPEZ, Benjamin; O'ROURKE, Patrick H.; SIDNEY, John; CERPAS, Cristhiam; BALMASEDA, Angel; SILVEIRA, Cassia G. T.; MAESTRI, Alvino; COSTA, Priscilla R.; DURBIN, Anna P.; DIEHL, Sean A.; PHILLIPS, Elizabeth; MALLAL, Simon; SILVA, Aruna D. De; NCHINDA, Godwin; NKENFOU, Celine; COLLINS, Matthew H.; SILVA, Aravinda M. de; LIM, Mei Qiu; MACARY, Paul A.; TATULLO, Filippo; SOLOMON, Tom; SATCHIDANANDAM, Vijaya; DESAI, Anita; RAVI, Vasanthapram; COLOMA, Josefina; TURTLE, Lance; RIVINO, Laura; KALLAS, Esper G.; PETERS, Bjoern; HARRIS, Eva; SETTE, Alessandro; WEISKOPF, Daniela
    Background: Dengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV). To enable global assessment of CD4(+) T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4(+) T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua. Methods: HLA class II epitopes in the population of Managua were identified by an in vitro IFN gamma ELISPOT assay. CD4(+) T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a ""megapool"" (MP) consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP(180) was validated by intracellular cytokine staining assays. Results: We detected responses directed against a total of 431 epitopes, representing all 4 DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4(+) T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka, and U.S. domestic flavivirus-naive subjects immunized with Tetravalent Dengue Live-Attenuated Vaccine (TV005). This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80% of alleles present with a phenotypic frequency >= 5% worldwide, corresponding to 92% phenotypic coverage of the general population (i.e., 92% of individuals express at least one of these alleles). Conclusion: The DENV CD4 MP180 can be utilized to measure ex vivo responses to DENV irrespective of geographical location.
  • article 41 Citação(ões) na Scopus
    Predictors of mortality in patients with yellow fever: an observational cohort study
    (2019) KALLAS, Esper G.; ZANELLA, Luiz Gonzaga F. A. B. D'Elia; V, Carlos Henrique Moreira; BUCCHERI, Renata; DINIZ, Gabriela B. F.; CASTINEIRAS, Anna Carla P.; COSTA, Priscilla R.; DIAS, Juliana Z. C.; MARMORATO, Mariana P.; SONG, Alice T. W.; MAESTRI, Alvino; BORGES, Igor C.; JOELSONS, Daniel; CERQUEIRA, Natalia B.; SOUZA, Nathalia C. Santiago e; CLARO, Ingra Morales; SABINO, Ester C.; LEVI, Jose Eduardo; I, Vivian Avelino-Silva; HO, Yeh-Li
    Background Yellow fever virus infection results in death in around 30% of symptomatic individuals. The aim of this study was to identify predictors of death measured at hospital admission in a cohort of patients admitted to hospital during the 2018 outbreak of yellow fever in the outskirts of Sao Paulo city, Brazil. Methods In this observational cohort study, we enrolled patients with yellow fever virus from two hospitals in Sao Paolo-the Hospital das Clinicas, University of Sao Paulo and the Infectious Diseases Institute ""Emilio Ribas"". Patients older than 18 years admitted to hospital with fever or myalgia, headache, arthralgia, oedema, rash, or conjunctivitis were consecutively screened for inclusion in the present study. Consenting patients were included if they had travelled to geographical areas in which yellow fever virus cases had been previously confirmed. Yellow fever infection was confirmed by real-time PCR in blood collected at admission or tissues at autopsy. We sequenced the complete genomes of yellow fever virus from infected individuals and evaluated demographic, clinical, and laboratory findings at admission and investigated whether any of these measurements correlated with patient outcome (death). Findings Between Jan 11, 2018, and May 10, 2018, 118 patients with suspected yellow fever were admitted to Hospital das Clinicas, and 113 patients with suspected yellow fever were admitted to Infectious Diseases Institute ""Emilio Ribas"". 95 patients with suspected yellow fever were included in the study, and 136 patients were excluded. Three (3%) of 95 patients with suspected yellow fever who were included in the study were excluded because they received a different diagnosis, and 16 patients with undetectable yellow fever virus RNA were excluded. Therefore, 76 patients with confirmed yellow fever virus infection, based on detectable yellow fever virus RNA in blood (74 patients) or yellow fever virus confirmed only at the autopsy report (two patients), were included in our analysis. 27 (36%) of 76 patients died during the 60 day period after hospital admission. We generated 14 complete yellow fever virus genomes from the first 15 viral load-detectable samples. The genomes belonged to a single monophyletic clade of the South America I genotype, sub-genotype E. Older age, male sex, higher leukocyte and neutrophil counts, higher alanine aminotransferase, aspartate transaminase (AST), bilirubin, and creatinine, prolonged prothrombin time, and higher yellow fever virus RNA plasma viral load were associated with higher mortality. In a multivariate regression model, older age, elevated neutrophil count, increased AST, and higher viral load remained independently associated with death. All 11 (100%) patients with neutrophil counts of 4000 cells per mL or greater and viral loads of 5.1 log(10) copies/mL or greater died (95% CI 72-100), compared with only three (11%) of 27 (95% CI 2-29) among patients with neutrophil counts of less than 4000 cells per mL and viral loads of less than 5.1 log(10) copies/mL. Interpretation We identified clinical and laboratory predictors of mortality at hospital admission that could aid in the care of patients with yellow fever virus. Identification of these prognostic markers in patients could help clinicians prioritise admission to the intensive care unit, as patients often deteriorate rapidly. Moreover, resource allocation could be improved to prioritise key laboratory examinations that might be more useful in determining whether a patient could have a better outcome. Our findings support the important role of the virus in disease pathogenesis, suggesting that an effective antiviral could alter the clinical course for patients with the most severe forms of yellow fever.
  • article 9 Citação(ões) na Scopus
    Humoral and cellular immune responses to CoronaVac up to one year after vaccination
    (2022) COSTA, Priscilla Ramos; CORREIA, Carolina Argondizo; MARMORATO, Mariana Prado; DIAS, Juliana Zanatta de Carvalho; THOMAZELLA, Mateus Vailant; SILVA, Amanda Cabral da; OLIVEIRA, Ana Carolina Soares de; GUSMAO, Arianne Fagotti; FERRARI, Lilian; FREITAS, Angela Carvalho; PATINO, Elizabeth Gonzalez; GRIFONI, Alba; WEISKOPF, Daniela; SETTE, Alessandro; SCHARF, Rami; KALLAS, Esper Georges; SILVEIRA, Cassia Gisele Terrassani
    Coronavac is a widely used SARS-CoV-2 inactivated vaccine, but its long-term immune response assessment is still lacking. We evaluated SARS-CoV-2-specific immune responses, including T cell activation markers, antigen-specific cytokine production and antibody response following vaccination in 53 adult and elderly individuals participating in a phase 3 clinical trial. Activated follicular helper T (Tfh), non-Tfh and memory CD4(+) T cells were detected in almost all subjects early after the first vaccine dose. Activated memory CD4(+) T cells were predominantly of central and effector memory T cell phenotypes and were sustained for at least 6 months. We also detected a balanced Th1-, Th2- and Th17/Th22-type cytokine production that was associated with response over time, together with particular cytokine profile linked to poor responses in older vaccinees. SARS-CoV-2-specific IgG levels peaked 14 days after the second dose and were mostly stable over one year. CoronaVac was able to induce a potent and durable antiviral antigen-specific cellular response and the cytokine profiles related to the response over time and impacted by the senescence were defined.
  • article 7 Citação(ões) na Scopus
    Asymptomatic anorectal Chlamydia trachomatis and Neisseria gonorrhoeae infections are associated with systemic CD8(+) T-cell activation
    (2017) VIEIRA, Vinicius A.; AVELINO-SILVA, Vivian I.; CERQUEIRA, Natalia B.; COSTA, Dayane A.; COSTA, Priscilla R.; VASCONCELOS, Ricardo P.; MADRUGA, Valdez R.; MOREIRA, Ronaldo I.; HOAGLAND, Brenda; VELOSO, Valdilea G.; GRINSZTEJN, Beatriz; KALLAS, Esper G.
    Background: Oral preexposure prophylaxis (PrEP) has been established as a pivotal strategy in HIV prevention. However, bacterial sexually transmitted infections (STIs), such as Chlamydia trachomatis and Neisseria gonorrhoeae, are also highly prevalent. Although the presence of STI-related mucosal lesions is a known risk factor for HIV acquisition, the potential increase in risk associated with asymptomatic STIs is not completely understood. Recent data demonstrated higher T-cell activation is a risk factor for sexually acquired HIV-1 infection. We examined the effect of asymptomatic C. trachomatis and N. gonorrhoeae anorectal infection on systemic immune activation, potentially increasing the risk of HIV acquisition. Methods: We analyzed samples from participants of PrEP Brasil, a demonstration study of daily oral emtricitabine/tenofovir disoproxil fumarate HIV PrEP among healthy MSM, for T-cell activation by flow cytometry. We included 34 asymptomatic participants with anorectal swab for C. trachomatis and/or N. gonorrhoeae infection, whereas negative for other STIs, and 35 controls. Results: We found a higher frequency of human leukocyte antigen DR(+)CD3(+)CD8(+)T cells (1.5 vs. 0.9%, P<0.005) and with memory phenotype in the group with asymptomatic C. trachomatis and/or N. gonorrhoeae infection. Exhaustion and senescence markers were also significant higher in this group. No difference was observed in the soluble CD14 levels. Conclusion: Our findings suggest asymptomatic anorectal C. trachomatis and/or N. gonorrhoeae increase systemic immune activation, potentially increasing the risk of HIV acquisition. Regular screening and treatment of asymptomatic STIs should be explored as adjuvant tools for HIV prevention.
  • article 31 Citação(ões) na Scopus
    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.