RESUMO
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.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Envelhecimento , Genética , Alergia e Imunologia , Betacoronavirus , Linfócitos T CD4-Positivos , Metabolismo , Linhagem da Célula , Montagem e Desmontagem da Cromatina , Infecções por Coronavirus , Alergia e Imunologia , Síndrome da Liberação de Citocina , Alergia e Imunologia , Citocinas , Genética , Suscetibilidade a Doenças , Citometria de Fluxo , Métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Rearranjo Gênico , Sistema Imunitário , Biologia Celular , Alergia e Imunologia , Imunocompetência , Genética , Inflamação , Genética , Alergia e Imunologia , Espectrometria de Massas , Métodos , Pandemias , Pneumonia Viral , Alergia e Imunologia , Análise de Sequência de RNA , Análise de Célula Única , TranscriptomaRESUMO
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.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Envelhecimento , Genética , Alergia e Imunologia , Betacoronavirus , Linfócitos T CD4-Positivos , Metabolismo , Linhagem da Célula , Montagem e Desmontagem da Cromatina , Infecções por Coronavirus , Alergia e Imunologia , Síndrome da Liberação de Citocina , Alergia e Imunologia , Citocinas , Genética , Suscetibilidade a Doenças , Citometria de Fluxo , Métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Rearranjo Gênico , Sistema Imunitário , Biologia Celular , Alergia e Imunologia , Imunocompetência , Genética , Inflamação , Genética , Alergia e Imunologia , Espectrometria de Massas , Métodos , Pandemias , Pneumonia Viral , Alergia e Imunologia , Análise de Sequência de RNA , Análise de Célula Única , TranscriptomaRESUMO
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.