ABSTRACT
Background: Follicular helper T cells (Tfh) are pivotal in B cell responses. Activation of the purinergic receptor P2X7 on Tfh cells regulates their activity. We investigated the ATP-P2X7R axis in circulating Tfh (cTfh) cells during Respiratory Syncytial Virus (RSV) infection. Methods: We analyzed two cohorts: children with RSV infection (moderate, n=30; severe, n=21) and healthy children (n=23). We utilized ELISA to quantify the levels of PreF RSV protein-specific IgG antibodies, IL-21 cytokine, and soluble P2X7R (sP2X7R) in both plasma and nasopharyngeal aspirates (NPA). Additionally, luminometry was employed to determine ATP levels in plasma, NPA and supernatant culture. The frequency of cTfh cells, P2X7R expression, and plasmablasts were assessed by flow cytometry. To evaluate apoptosis, proliferation, and IL-21 production by cTfh cells, we cultured PBMCs in the presence of Bz-ATP and/or P2X7R antagonist (KN-62) and a flow cytometry analysis was performed. Results: In children with severe RSV disease, we observed diminished titers of neutralizing anti-PreF IgG antibodies. Additionally, severe infections, compared to moderate cases, were associated with fewer cTfh cells and reduced plasma levels of IL-21. Our investigation revealed dysregulation in the ATP-P2X7R pathway during RSV infection. This was characterized by elevated ATP levels in both plasma and NPA samples, increased expression of P2X7R on cTfh cells, lower levels of sP2X7R, and heightened ATP release from PBMCs upon stimulation, particularly evident in severe cases. Importantly, ATP exposure decreased cTfh proliferative response and IL-21 production, while promoting their apoptosis. The P2X7R antagonist KN-62 mitigated these effects. Furthermore, disease severity positively correlated with ATP levels in plasma and NPA samples and inversely correlated with cTfh frequency. Conclusion: Our findings indicate that activation of the ATP-P2X7R pathway during RSV infection may contribute to limiting the cTfh cell compartment by promoting cell death and dysfunction, ultimately leading to increased disease severity.
Subject(s)
Adenosine Triphosphate , Receptors, Purinergic P2X7 , Respiratory Syncytial Virus Infections , T Follicular Helper Cells , Humans , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/metabolism , Receptors, Purinergic P2X7/metabolism , Adenosine Triphosphate/metabolism , Male , Infant , Female , T Follicular Helper Cells/immunology , T Follicular Helper Cells/metabolism , Child, Preschool , Signal Transduction , Interleukins/metabolism , Interleukins/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Child , Respiratory Syncytial Virus, Human/immunologyABSTRACT
Determinar el nivel de información sobre factores de riesgo de Infarto agudo de miocardio en los pacientes ambulatorios que asisten a una institución de salud de la provincia de Corrientes año 2021. Metodología: Estudio cuantitativo descriptivo, transversal y observacional. Muestra obtenida mediante muestreo probabilístico aleatorio simple compuesta por 108 pacientes que asistieron a los consultorios de Diabetes, Presurometría y Hospital de Día. Se aplicó un cuestionario validado mediante una prueba piloto. Variables: edad, sexo, nivel de instrucción, Nivel de información sobre alimentación, hábitos nocivos, actividad física y preguntas generales. Los resultados fueron volcados a una matriz diseñada en programa Excel. Resultados: La población en estudio presento una mediana de edad de 43, moda 39 y predomino del sexo masculino 56%, sobre el femenino 44%, en el nivel de instrucción prevaleció el secundario completo 19% seguido de primario incompleto 15%. Abordando los niveles de información sobre factores de riesgo de Infarto agudo de miocardio predominaron los niveles altos en todas las variables trabajadas, obteniendo un nivel general de información alto del 82%, se apreció en la alimentación 65%, hábitos nocivos 70%, aspectos generales un 86% y actividad física 48%. Conclusión: Esta investigación remarca la importancia de la educación permanente y en etapas tempranas sobre los factores de riesgo de Infarto Agudo de Miocardio. La población en estudio presento un nivel alto de información. No obstante, la educación debe fomentarse para llegar al 37% restante que obtuvo niveles inferiores[AU]
To determine the level of information on risk factors for acute myocardial infarction in outpatients attending a health institution in the province of Corrientes in 2021. Methodology: Quantitative descriptive, cross-sectional and observational study. Sample obtained by simple random probabilistic sampling made up of 108 patients who attended the Diabetes, Blood Pressure and Day Hospital clinics. A validated questionnaire was applied by means of a pilot test. Variables: age, sex, level of education, level of information on food, harmful habits, physical activity and general questions. Te results were dumped into a matrix designed in Excel program. Results: Te population under study presented a median age of 43, mode 39 and a predominance of males 56%, over females 44%, on the level of education the complete secondary prevailed 19% followed by incomplete primary 15%. Addressing the levels of information on risk factors for acute myocardial infarction, high levels predominated in all the variables worked on, obtaining a high general level of information of 82%, disaggregating 65%, harmful habits 70%, aspects general 86% and physical activity 48%. Conclusion: Tis research highlights the importance of permanent education and in early stages about the risk factors of Acute Myocardial Infarction. Te study population presented a high level of information. However, education should be encouraged to reach the remaining 37% who obtained lower levels[AU]
: Determinar o nível de informação sobre fatores de risco para infarto agudo do miocárdio em pacientes ambulatoriais atendidos em uma instituição de saúde na província de Corrientes em 2021. Metodologia: Estudo quantitativo descritivo, transversal e observacional. Amostra obtida por amostragem probabilística aleatória simples composta por 108 pacientes atendidos nas clínicas de Diabetes, Pressão Arterial e Hospital Dia. Foi aplicado um questionário validado por meio de teste piloto. Variáveis: idade, sexo, escolaridade, nível de informação sobre alimentação, hábitos nocivos, atividade física e questões gerais. Os resultados foram despejados em uma matriz projetada no programa Excel. Resultados: A população em estudo apresentou mediana de idade de 43 anos, moda 39 e predominância do sexo masculino 56%, sobre o feminino 44%, no nível de escolaridade o ensino médio completo prevaleceu 19% seguido do ensino fundamental incompleto 15%. Abordando os níveis de informação sobre fatores de risco para infarto agudo do miocárdio, predominaram níveis elevados em todas as variáveis trabalhadas, obtendo um nível geral de informação elevado de 82%, desagregando 65%, hábitos nocivos 70%, aspectos gerais 86% e atividade física 48%. Conclusão: Esta pesquisa destaca a importância da educação permanente e precoce sobre os fatores de risco do Infarto Agudo do Miocárdio. A população do estudo apresentou um alto nível de informação. No entanto, a educação deve ser incentivada para atingir os 37% restantes que obtiveram níveis mais baixos[AU]
