RESUMEN
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Adulto Joven , Envejecimiento , Genética , Alergia e Inmunología , Betacoronavirus , Linfocitos T CD4-Positivos , Metabolismo , Linaje de la Célula , Ensamble y Desensamble de Cromatina , Infecciones por Coronavirus , Alergia e Inmunología , Síndrome de Liberación de Citoquinas , Alergia e Inmunología , Citocinas , Genética , Susceptibilidad a Enfermedades , Citometría de Flujo , Métodos , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Reordenamiento Génico , Sistema Inmunológico , Biología Celular , Alergia e Inmunología , Inmunocompetencia , Genética , Inflamación , Genética , Alergia e Inmunología , Espectrometría de Masas , Métodos , Pandemias , Neumonía Viral , Alergia e Inmunología , Análisis de Secuencia de ARN , Análisis de la Célula Individual , TranscriptomaRESUMEN
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Adulto Joven , Envejecimiento , Genética , Alergia e Inmunología , Betacoronavirus , Linfocitos T CD4-Positivos , Metabolismo , Linaje de la Célula , Ensamble y Desensamble de Cromatina , Infecciones por Coronavirus , Alergia e Inmunología , Síndrome de Liberación de Citoquinas , Alergia e Inmunología , Citocinas , Genética , Susceptibilidad a Enfermedades , Citometría de Flujo , Métodos , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Reordenamiento Génico , Sistema Inmunológico , Biología Celular , Alergia e Inmunología , Inmunocompetencia , Genética , Inflamación , Genética , Alergia e Inmunología , Espectrometría de Masas , Métodos , Pandemias , Neumonía Viral , Alergia e Inmunología , Análisis de Secuencia de ARN , Análisis de la Célula Individual , TranscriptomaRESUMEN
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Adulto Joven , Envejecimiento , Genética , Alergia e Inmunología , Betacoronavirus , Linfocitos T CD4-Positivos , Metabolismo , Linaje de la Célula , Ensamble y Desensamble de Cromatina , Infecciones por Coronavirus , Alergia e Inmunología , Síndrome de Liberación de Citoquinas , Alergia e Inmunología , Citocinas , Genética , Susceptibilidad a Enfermedades , Citometría de Flujo , Métodos , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Reordenamiento Génico , Sistema Inmunológico , Biología Celular , Alergia e Inmunología , Inmunocompetencia , Genética , Inflamación , Genética , Alergia e Inmunología , Espectrometría de Masas , Métodos , Pandemias , Neumonía Viral , Alergia e Inmunología , Análisis de Secuencia de ARN , Análisis de la Célula Individual , TranscriptomaRESUMEN
@#The purification of parasite-infected erythrocytes from whole blood containing leucocytes is crucial for many downstream genetic and molecular assays in parasitology. Current methodologies to achieve this are often costly and time consuming. Here, we demonstrate the successful application of a cheap and simple Non-Woven Fabric (NWF) filter for the purification of parasitized red blood cells from whole blood. NWF filtration was applied to the malaria-parasitized blood of three strains of mice, and one strain of rat, and to Babesia gibsoni parasitized dog blood. Before and after filtration, the white blood cell (WBC) removal rates and red blood cell (RBC) recovery rates were measured. After NWF filter treatment of rodent malaria-infected blood, the WBC removal rates and RBC recovery rates were, for Kunming mice: 99.51%±0.30% and 86.12%±8.37%; for BALB/C mice: 99.61%±0.15% and 80.74%±7.11%; for C57 mice: 99.71%±0.12% and 84.87%±3.83%; for Sprague-Dawley rats: 99.93%±0.03% and 83.30%±2.96%. Microscopy showed WBCs were efficiently removed from infected dog blood samples, and there was no obvious morphological change of B. gibsoni parasites. NWF filters efficiently remove leukocytes from malaria parasite-infected mouse and rat blood, and are also suitable for filtration of B. gibsoni-infected dog blood.
RESUMEN
Alveolar epithelia play an essential role in maintaining the integrity and homeostasis of lungs, in which alveolar epithelial type II cells (AECII) are a cell type with stem cell potential for epithelial injury repair and regeneration. However, mechanisms behind the physiological and pathological roles of alveolar epithelia in human lungs remain largely unknown, partially owing to the difficulty of isolation and culture of primary human AECII cells. In the present study, we aimed to characterize alveolar epithelia generated from A549 lung adenocarcinoma cells that were cultured in an air-liquid interface (ALI) state. Morphological analysis demonstrated that A549 cells could reconstitute epithelial layers in ALI cultures as evaluated by histochemistry staining and electronic microscopy. Immunofluorescent staining further revealed an expression of alveolar epithelial type I cell (AECI) markers aquaporin-5 protein (AQP-5), and AECII cell marker surfactant protein C (SPC) in subpopulations of ALI cultured cells. Importantly, molecular analysis further revealed the expression of AQP-5, SPC, thyroid transcription factor-1, zonula occludens-1 and Mucin 5B in A549 ALI cultures as determined by both immunoblotting and quantitative RT-PCR assay. These results suggest that the ALI culture of A549 cells can partially mimic the property of alveolar epithelia, which may be a feasible and alternative model for investigating roles and mechanisms of alveolar epithelia in vitro.
Asunto(s)
Humanos , Medios de Cultivo Condicionados , Técnicas de Cultivo de Célula/métodos , Células Epiteliales Alveolares/fisiología , Células A549/fisiología , Valores de Referencia , Factores de Tiempo , Microscopía Electrónica de Rastreo , Immunoblotting , Recuento de Células , Reproducibilidad de los Resultados , Análisis de Varianza , Proteína C Asociada a Surfactante Pulmonar/análisis , Acuaporina 5/análisis , Mucina 5B/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteína de la Zonula Occludens-1/análisis , Factor Nuclear Tiroideo 1/análisisAsunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/cirugía , Neoplasias Renales/epidemiología , Neoplasias Renales/cirugía , Nefrectomía/efectos adversos , Nefrectomía/estadística & datos numéricos , Comorbilidad , Bases de Datos Factuales , Tasa de Filtración Glomerular , Incidencia , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Complicaciones Posoperatorias/epidemiología , Proteinuria/epidemiología , Factores de RiesgoRESUMEN
This paper presents the results of a study on simplified surveillance methods conducted in 23 pilot counties in 11 provinces and municipalities in China where reside 15 million people and malaria control has been in the late consolidation phase. Two simplified surveillance Schemes (A and B) taking treatment of clinical cases as the main measure were implemented in 1992-1994. The rate of annual blood examination for case detection was 1.0% in pilot Scheme A, while in areas of scheme B it was 0.3%. The implementation of both Scheme A and Scheme B, simplified or without treatment of infection foci and management of mobile populations, acquired satisfactory effects against malaria. Consequently, malaria incidence was declining steadily, only a few indigenous and introduced cases were detected. The parasite rate in residents and the IFA positive rate in children were very low. The results of pilot studies and cost-effectiveness analysis indicated that Scheme B is effective, rational and economic, and can be implemented to replace the routine surveillance measures in areas where malaria has been at the late consolidation phase in China.