Evaluation of three formulations based on Polymorphic membrane protein D in mice infected with Chlamydia trachomatis.

The significant impact of Chlamydia trachomatis(Ct) infections worldwide highlights the need to develop a prophylactic vaccine that elicits effective immunity and protects the host from the immunopathological effects of Ct infection. The aim of this study was to evaluate a vaccine based on a fragment of the Polymorphic membrane protein D (FPmpD) of C. trachomatis as an immunogen using a heterologous DNA prime-protein boost strategy in female mice Three different formulations were evaluated as protein boost: free recombinant FPmpD (rFPmpD) or rFPmpD formulated with a liposomal adjuvant alternatively supplemented with CpG or a cationic gemini lipopeptide as immunostimulants. The three candidates induced an increase in the cervicovaginal and systemic titers of anti-rFPmpD antibodies in two strains of mice (BALB/c and C57BL/6), with no evidence of fertility alterations. The three formulations induced a rapid and robust humoral immune response upon the Ct challenge. However, the booster with free rFPmpD more efficiently reduced the shedding of infective Ct and prevented the development of immunopathology. The formulations containing adjuvant induced a strong inflammatory reaction in the uterine tissue. Hence, the prime-boost strategy with the adjuvant-free FPmpD vaccine formulation might constitute a promissory candidate to prevent C. trachomatis intravaginal infection.

Heterologous prime-boost vaccination based on Polymorphic protein D protects against intravaginal Chlamydia trachomatis infection in mice.

The control of the worldwide spread of sexually transmitted Chlamydia trachomatis (Ct) infection urgently demands the development of a preventive vaccine. In this work, we designed a vaccine based on a fragment of polymorphic protein D (FPmpD) that proved to be immunogenic enough to generate a robust systemic and mucosal IgG humoral immune response in two strains of mice. We used a heterologous prime-boost strategy, including simultaneous systemic and mucosal administration routes. The high titers of anti-PmpD antibodies elicited by this immunization scheme did not affect murine fertility. We tested the vaccine in a mouse model of Ct intravaginal infection. Anti-PmpD antibodies displayed potent neutralizing activity in vitro and protective effects in uterine tissues in vivo. Notably, the humoral immune response of PmpD-vaccinated mice was faster and stronger than the primary immune response of non-vaccinated mice when exposed to Ct. FPmpD-based vaccine effectively reduced Ct shedding into cervicovaginal fluids, bacterial burden at the genitourinary tract, and overall infectivity. Hence, the FPmpD-based vaccine might constitute an efficient tool to protect against Ct intravaginal infection and decrease the infection spreading.

Chlamydia trachomatis Infection Impairs MHC-I Intracellular Trafficking and Antigen Cross-Presentation by Dendritic Cells.

During cross-presentation, exogenous antigens (i.e. intracellular pathogens or tumor cells) are internalized and processed within the endocytic system and also by the proteasome in the cytosol. Then, antigenic peptides are associated with Major Histocompatibility Complex (MHC) class I molecules and these complexes transit to the plasma membrane in order to trigger cytotoxic immune responses through the activation of CD8+ T lymphocytes. Dendritic cells (DCs) are particularly adapted to achieve efficient antigen cross-presentation and their endocytic network displays important roles during this process, including a sophisticated MHC-I transport dependent on recycling compartments. In this study, we show that C. trachomatis, an obligate intracellular pathogen that exhibits multiple strategies to evade the immune system, is able to induce productive infections in the murine DC line JAWS-II. Our results show that when C. trachomatis infects these cells, the bacteria-containing vacuole strongly recruits host cell recycling vesicles, but no other endosomal compartments. Furthermore, we found that chlamydial infection causes significant alterations of MHC-I trafficking in JAWS-II DCs: reduced levels of MHC-I expression at the cell surface, disruption of the perinuclear MHC-I intracellular pool, and impairment of MHC-I endocytic recycling to the plasma membrane. We observed that all these modifications lead to a hampered cross-presentation ability of soluble and particulate antigens by JAWS-II DCs and primary bone marrow-derived DCs. In summary, our findings provide substantial evidence that C. trachomatis hijacks the DC endocytic recycling system, causing detrimental changes on MHC-I intracellular transport, which are relevant for competent antigen cross-presentation.

Relación entre estradiol plasmático, glucemia en ayunas y triglicéridos en varones con síndrome metabólico / Relationship between plasma oestradiol, fasting glucose, and triglycerides in males with metabolic syndrome

Introducción: En varones, el estradiol circula en pequeñas concentraciones (8-40 pg/ml), sin estar del todo claras aún sus funciones. En este contexto, es necesario aclarar los efectos de esta hormona en el sexo masculino. Además de estudiarse el posible papel en la reproducción masculina, en los últimos años se ha tratado de encontrar la relación entre sus niveles y los componentes del síndrome metabólico. Sin embargo, la bibliografía existente no aclara si ejerce un papel protector o perjudicial con respecto a dicha patología. Objetivos: Analizar las relaciones existentes entre el estradiol y los componentes del síndrome metabólico en una muestra de varones excedidos de peso con síndrome metabólico de la provincia de Mendoza. Metodología: Se estudió a 40 varones con sobrepeso u obesidad y síndrome metabólico residentes en la ciudad de Mendoza, con edades entre 53 y 74 años, los cuales fueron evaluados a partir de una consulta médica de rutina. Se determinaron estradiol, testosterona, glucemia en ayunas, insulina en ayunas, índice HOMA, perfil lipídico y ácido úrico. Se evaluó el estado nutricional mediante antropometría: peso, talla, circunferencias, pliegues cutáneos y medidas derivadas. El análisis estadístico se realizó mediante correlación de Pearson o Spearman según la normalidad de las variables y la prueba de la t de Student para muestras independientes. Se utilizó un nivel mínimo de significación de p < 0,05. Resultados: Los niveles de estradiol se correlacionaron negativamente con los valores de triglicéridos (r = -0,401; p = 0,013) y con la glucemia en ayunas (r= -0,333; p= 0,041). Por otra parte, los individuos normotrigliceridémicos (valor de triglicéridos < 150 mg/dl) mostraron valores mayores de estradiol que los hipertrigliceridémicos (p = 0,02). Conclusiones: Los niveles de estradiol muestran relación inversa con triglicéridos y glucemia en ayunas en varones con síndrome metabólico.

Introduction: Oestradiol circulates in low concentrations (8-40 pg/ml) in males, with its functions still not being entirely clear. In this context, there is a need to determine the effects it has on males. Apart from studying the potential role oestradiol has on male reproduction in recent years, efforts have been made to determine the relationship between oestradiol levels and metabolic syndrome components. Nevertheless, the existing bibliography does not clarify whether oestradiol plays a protective or detrimental role in this condition. Objectives: The present work aimed to analyse the relationship between serum oestradiol levels and metabolic syndrome components in overweight men from Mendoza. Methodology: The sample consisted of 40 overweight or obese males, aged 53-74, with metabolic syndrome, and living in the city of Mendoza. Based on a health routine check-up, they were evaluated by determining the levels of oestradiol, testosterone, fasting blood glucose, insulin, HOMA index, lipid profile, and uric acid. Nutritional status was assessed using anthropometric measurements: weight, height, circumferences, and skinfold thickness. Statistical analysis was carried out using Pearson or Spearman correlation according to the normality of variables and the Student t test for independent samples. A minimum level of significance of P<.05 was used. Results: Oestradiol levels negatively correlated with triglyceride values (r = -0.401; P=.013) and fasting blood glucose (r= -0.333; P=.041). Furthermore, those with normal triglycerides (triglyceride values <150 mg/dl) showed higher oestradiol levels compared to those with high triglycerides (P=.02). Conclusions: Oestradiol levels show an inverse relationship as regards triglycerides and fasting blood glucose in men with metabolic syndrome.

[Lipid - lowering effect of mate tea intake in dyslipidemic subjects]. / EFECTO HIPOLIPEMIANTE DEL CONSUMO DE MATE EN INDIVIDUOS DISLIPIDÉMICOS.

INTRODUCTION: Mate is the national infusion of Argentina and its properties on human health have not been fully elucidated. OBJECTIVE: To evaluate changes in lipid profile in dyslipidemic patients supplemented with yerba mate. METHODS: 121 dyslipidemic subjects (total cholesterol (TC), LDL cholesterol (LDLC) cholesterol and / or triglycerides (TG) elevated) without lipid-lowering therapy, both sexes (74 women and 47 men) between 40 and 60 years old were studied. After six weeks of mate abstinence, lipid profile and atherogenic index (AI), body composition by anthropometry and recent intake of energy, nutrients and food groups by food frequency questionnaire were analyzed. Daily consumption of mate prepared with 50 g or 100 g of yerba mate was indicated, plus the instruction not to alter eating habits, smoking, medication or exercise. All determinations were repeated after six and twelve weeks. Statistical analysis was performed using Student's T test for paired samples or Wilcoxon test according to normality of the variables (p <0.05). RESULTS: At the end of twelve weeks, TC fell 9.49% (21.66 mg/dL), LDLC fell 11.95% (17.96 mg/dL) HDLC fell 3.34% (1.65 mg/dL) and AI dropped 6.58% (0.31 points), p <0.001 for all cases. TG decreased 7.02% (10.74 mg/dl; p = 0.029) only in 50 g yerba mate consumers. Anthropometric and nutritional variables did not change significantly. CONCLUSIONS: Daily consumption of mate produces a time-dependent decrease in TC and its fractions in dyslipidemic subjects.

Introducción: El mate es la infusión nacional de Argentina y sus propiedades en la salud humana no han sido totalmente aclaradas. Objetivos: Evaluar las modificaciones del perfil lipídico en pacientes dislipidémicos suplementados con yerba mate. Métodos: Se estudiaron 121 individuos dislipidémicos (Colesterol Total (CT), Colesterol LDL (CLDL) y/o Triglicéridos (TG) elevados) de ambos sexos (74 mujeres y 47 varones) entre 40 y 60 años, sin tratamiento hipolipemiante. Luego de seis semanas de abstinencia de mate, se analizó su perfil lipídico e índice aterogénico (IA), composición corporal a través de antropometría y consumo reciente de energía, nutrientes y grupos de alimentos a través de cuestionario de frecuencia de consumo. Se indicó el consumo diario de mate preparado con 50g o 100g de yerba mate. Se indicó no alterar hábitos alimentarios, tabaquismo, medicación ni ejercicio físico. Se repitieron las determinaciones luego de seis y doce semanas. El análisis estadístico se realizó mediante prueba T de Student para muestras relacionadas o prueba de Wilcoxon según normalidad de las variables (p.