http://www.bdtd.uerj.br/handle/1/3561 2026-05-11T18:42:12Z http://www.bdtd.uerj.br/handle/1/25566 Título: Avaliação da influência da obesidade materna no desenvolvimento de resposta humoral no baço da prole em modelo experimental murino Autor: Durão, César Vieira Primeiro orientador: Silva, Flávia Márcia de Castro e Abstract: INTRODUCTION: The increase in maternal obesity cases has raised significant concern, as it is associated with a higher overall mortality rate and represents a major risk factor for several diseases. During pregnancy, this condition can trigger metabolic changes that influence fetal development, impacting various systems, including the immune system. OBJECTIVE: This study aimed to evaluate the influence of maternal obesity on the development of the humoral immune response in the offspring’s spleen. METHODS: A murine experimental model using BALB/c mice was employed. Females were subjected to a high-fat diet (60% of calories derived from fat) for ten weeks and subsequently mated. Offspring were selected at different ages (1, 3, 7, and 24 days of life) for experimental procedures, in which the spleen and serum were collected for analysis of cell phenotypes by flow cytometry, histology, and detection of antibody isotypes by ELISA. RESULTS: Flow cytometry analyses revealed differences in the frequency of cell groups and in the membrane molecule expression of splenic cells. On the first day of life, an increase in B lymphocytes and a reduction in CD19⁺CD138⁺ plasma cells were observed in offspring from obese mothers compared to the control group. On the seventh day, there was an increase in B lymphocytes and MHCII expression in these cells, along with a reduction in CD19⁺CD138⁺IgG2a⁺ plasma cells and T lymphocytes expressing CXCR5. By the twenty-fourth day of life, B lymphocytes, plasma cells, and T lymphocytes were increased; however, MHCII and PD-L1 expression was reduced in CD19⁺ cell populations. Additionally, histological evaluation showed a greater number of lymphoid follicles and a lower eosinophil count in the offspring of obese mothers. A reduction in serum immunoglobulin isotypes IgM and IgG was detected in these animals, although an increase in IgG1 and IgG2a isotypes was observed in the more developmentally advanced group. CONCLUSION: The results demonstrate that maternal obesity affects the development of the humoral immune response in the offspring, compromising immune activation. The reduction of T lymphocytes and the low serum levels of IgG and IgM suggest impairments in class switching and immunological memory. These changes may result in a less efficient immune response, potentially leading to more prolonged infections. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação 2026-04-04T00:00:00Z http://www.bdtd.uerj.br/handle/1/25501 Título: Tipificação molecular e análise da resistência aos antimicrobianos em Acinetobacter spp. recuperados do período pré-pandêmico e pandêmico da COVID-19 Autor: Rosa, Heloisa da Silva Primeiro orientador: Marques, Elizabeth de Andrade Abstract: Acinetobacter spp. are nosocomial pathogens that present a significant public health challenge due to their ability to resist disinfection and desiccation, primarily attributed to the rising incidence of multidrug-resistant strains, thereby limiting therapeutic options. Throughout the COVID-19 pandemic, Acinetobacter spp. emerged as a prominent pathogen linked to secondary infections, resulting in prolonged stays in the ICU and heightened patient mortality. Therefore, this study aims to evaluate the antimicrobial resistance profile, its correlation with carbapenemase enzyme production, and the phylogenetic relationships among 60 Acinetobacter spp. samples retrieved from patients hospitalized at a university hospital in Rio de Janeiro during both the pre-pandemic and pandemic phases of COVID-19. Antimicrobial susceptibility tests were conducted using agar diffusion and broth microdilution methods. The detection of carbapenemase production was performed using the modified carbapenem inactivation method (mCIM) and the NG-TEST CARBA 5 immunochromatographic assay. The determination of the phylogenetic relationships among isolates was carried out using pulsed-field gel electrophoresis (PFGE). Whole-genome sequencing (WGS) of selected samples was performed to identify the species, determine the sequence type (ST), and detect polymyxin B resistance determinants. Out of the 60 samples tested, 58.3% (n = 35) exhibited resistance to all tested antimicrobials. Only one isolate displayed a multidrug-resistant (MDR) phenotype, and 95% (n = 57) demonstrated extensively drug-resistant (XDR) profiles. Minimum inhibitory concentration values for polymyxin B ranged from 0.25 to 4µg/mL. Through the mCIM, 52 carbapenemase-producing isolates were detected, and through the NG-TEST CARBA 5, 20 isolates were found to produce the IMP carbapenemase. Thirty-six pulsotypes were identified, with pulsotype L being the most prevalent, comprising ten isolates. WGS of isolates 22319 and 22718 was conducted due to polymyxin B resistance and susceptibility to other tested antimicrobials. The analysis of WGS data revealed that both isolates were identified as Acinetobacter nosocomialis, with 22319 associated with ST 395 and 22718 with the new ST 2261, characterized in this study. These isolates did not belong to any clonal complex. Both isolates exhibited mutations in the lpsB, lpxC, and lptD genes, while 22718 also displayed mutations in lpxD and pldA, potentially linked to polymyxin B resistance. The mcr gene was not detected. These results signify a widespread epidemiological profile in Brazil and worldwide, where the high rate of antimicrobial resistance and the presence of carbapenemases are alarming. Further studies are imperative to formulate measures for the control and prevention of healthcare-associated infections caused by these microorganisms. Additionally, polymyxin B resistance may be associated with mutations in the lpsB, lpxC, lpxD, lptD, and pldA genes; however, additional studies are required to comprehend the significance and contribution of these mutations to polymyxin B resistance. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação 2023-12-12T00:00:00Z http://www.bdtd.uerj.br/handle/1/25475 Título: Estudo da esquistossomose mansônica associada a dislipidemia em modelo experimental: Implicações no fígado, tecido adiposo e nos helmintos após tratamento com praziquantel Autor: Ubirajara, Thainá de Melo Primeiro orientador: Neves, Renata Heisler Abstract: Schistosomiasis is a neglected disease affecting millions of people in endemic areas, with its progression strongly influenced by the host’s metabolism, and praziquantel (PZQ) being the only available therapeutic option. In this context, the present study aimed to investigate the therapeutic response to PZQ in acute schistosomal infection, assessing remodeling of the liver and visceral adipose tissue, as well as the effects on Schistosoma mansoni recovered from mice subjected to a high-fat diet (HFD). Female mice received either an HFD or a standard diet, and after 24 weeks were infected with 100 S. mansoni cercariae (LE strain). At week 32, animals were treated with a single dose of 60 mg/kg PZQ. At week 34, animals were euthanized, and blood samples were collected for biochemical analyses. Peritoneal macrophage and splenic lymphocyte cultures were performed to evaluate cytokine profiles. Liver and adipose tissue were collected for histopathological, stereological, and morphometric analyses, with a portion of the liver reserved for assessment of hepatic bioenergetics and parasitic load. Worms were recovered from the portal and mesenteric veins, separated by sex, fixed, stained, and analyzed by microscopy. Results showed that the HFD induced metabolic and inflammatory alterations, including dyslipidemia, vascular remodeling, tissue inflammation, and disruption of hepatic architecture, although it also activated compensatory lipid oxidation pathways. S. mansoni infection modulated some of these effects, reducing plasma lipids and certain markers of liver injury, while simultaneously exacerbating metabolic stress, promoting mitochondrial dysfunction, vascular remodeling, and intense inflammation in the liver and adipose tissue, as well as supporting parasite reproduction and adaptation. PZQ treatment in mice fed a standard diet was safe and effective, reducing worm and egg burdens, inducing morphological changes in the parasite tegument, relieving hepatic metabolic stress, and remodeling adipose tissue. However, the HFD modulated the drug response, conferring greater protection to the parasite tegument, decreasing vascular displacement in the liver, and altering host metabolic and immune responses. This modulation resulted in less structural restoration in the liver and adipose tissue in animals on the HFD compared to those on a standard diet. These findings demonstrate that the host’s nutritional status directly influences the therapeutic efficacy of praziquantel, highlighting the importance of the metabolic context in the progression of schistosomiasis. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Tese 2025-10-10T00:00:00Z http://www.bdtd.uerj.br/handle/1/25331 Título: Impacto da infecção pelo HIV na resposta imune de crianças e adolescentes após imunização com a vacina conjugada meningocócica contra o sorogrupo C Autor: Silva, Giselle Pereira da Primeiro orientador: Milagres, Lucimar Gonçalves Abstract: Neisseria meningitidis serogroup C (MenC) has been the cause of outbreaks in Brazil since 2005. Vaccines conjugated against MenC are available in Brazil and are effective in immunologically normal patients, but little is known about the impact on HIV + patients. The main objective of this study was to analyze the response of neutralizing antibodies against diphtheria toxin induced by the conjugate vaccine, to investigate the influence of the expression of activation and inhibition markers on CD4 + T cells and to phenotypically characterize the circulating helper T cells (Tfh) and cells B and how these cells are associated with bactericidal antibody levels after immunization in HIV-infected children and adolescents responding to or not to the MenC conjugate vaccine (MCC). We report the association of anti-diphtheria neutralizing antibodies with bactericidal antibodies (SBA). Before vaccination, 50% HIV + patients had no protection against diphtheria and only 19% had complete protection. In HIV-infected individuals 56% had complete protection before immunization and 12% had no protection against diphtheria. After one and two immunizations, 96% of HIV- and 64% of HIV + showed complete protection against diphtheria. They indicate that CRM197 was able to induce a primary and / or reinforcement response in both groups of individuals. When assessing the expression of activation and inhibition markers, we observed that PD-1 and / or TIGIT expression was positively associated with CD4 + (HLA-DR + CD38 +) T cell activation and viral load but negatively correlated with response SBA in HIV + patients, as well as with the CD4-T cell count or percentage. Blood levels of IL-4 correlated positively with SBA titers, but negatively correlated with expression of the activation / inhibition markers. An opposite profile was observed for the chemokine CXCL-13. Suggesting that the expression of inhibitory and activation molecules may lead to poor response to the MCC vaccine in HIV + children and adolescents. By analyzing the phenotype of circulating Tfh cells and B cells we find that B cells depleted as well as short-lived plasmablast are increased in treated patients and negatively associated with MCC vaccine-induced SBA levels. The basal frequency of activated circulating Tfh cells correlated negatively with the SBA response but correlated positively with the frequency of circulating plasmablast cells. Baseline IL4 levels positively associated with the SBA response but showed a negative correlation with the frequency of activated circulating Tfh cells. Indicating that increased a frequency of circulating activated Tfh cells found in non-responders to the vaccine may imply that there is a greater activation / differentiation of CD4 + T cells within the lymph node. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Tese 2018-08-20T00:00:00Z