tetano
Editor, Senior Moderator
Cell Commun Signal
. 2021 Jul 8;19(1):73.
doi: 10.1186/s12964-021-00754-7.
Single-cell analysis reveals cell communication triggered by macrophages associated with the reduction and exhaustion of CD8 [SUP]+[/SUP] T cells in COVID-19
Lei He[SUP] #[/SUP][SUP] 1 [/SUP], Quan Zhang[SUP] #[/SUP][SUP] 2 [/SUP], Yue Zhang[SUP] 1 [/SUP], Yixian Fan[SUP] 3 [/SUP], Fahu Yuan[SUP] 4 [/SUP], Songming Li[SUP] 5 [/SUP]
Affiliations
Abstract
Background: The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has become an ongoing pandemic. Understanding the respiratory immune microenvironment which is composed of multiple cell types, together with cell communication based on ligand-receptor interactions is important for developing vaccines, probing COVID-19 pathogenesis, and improving pandemic control measures.
Methods: A total of 102 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study. Clinical information, routine laboratory tests, and flow cytometry analysis data with different conditions were collected and assessed for predictive value in COVID-19 patients. Next, we analyzed public single-cell RNA-sequencing (scRNA-seq) data from bronchoalveolar lavage fluid, which offers the closest available view of immune cell heterogeneity as encountered in patients with varying severity of COVID-19. A weighting algorithm was used to calculate ligand-receptor interactions, revealing the communication potentially associated with outcomes across cell types. Finally, serum cytokines including IL6, IL1β, IL10, CXCL10, TNFα, GALECTIN-1, and IGF1 derived from patients were measured.
Results: Of the 102 COVID-19 patients, 42 cases (41.2%) were categorized as severe. Multivariate logistic regression analysis demonstrated that AST, D-dimer, BUN, and WBC were considered as independent risk factors for the severity of COVID-19. T cell numbers including total T cells, CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells in the severe disease group were significantly lower than those in the moderate disease group. The risk model containing the above mentioned inflammatory damage parameters, and the counts of T cells, with AUROCs ranged from 0.78 to 0.87. To investigate the molecular mechanism at the cellular level, we analyzed the published scRNA-seq data and found that macrophages displayed specific functional diversity after SARS-Cov-2 infection, and the metabolic pathway activities in the identified macrophage subtypes were influenced by hypoxia status. Importantly, we described ligand-receptor interactions that are related to COVID-19 serverity involving macrophages and T cell subsets by communication analysis.
Conclusions: Our study showed that macrophages driving ligand-receptor crosstalk contributed to the reduction and exhaustion of CD8[SUP]+[/SUP] T cells. The identified crucial cytokine panel, including IL6, IL1β, IL10, CXCL10, IGF1, and GALECTIN-1, may offer the selective targets to improve the efficacy of COVID-19 therapy.
Trial registration: This is a retrospective observational study without a trial registration number. Video Abstract.
Keywords: COVID-19; Macrophage; SARS-CoV-2; Single cell RNA-sequencing; T cell.
. 2021 Jul 8;19(1):73.
doi: 10.1186/s12964-021-00754-7.
Single-cell analysis reveals cell communication triggered by macrophages associated with the reduction and exhaustion of CD8 [SUP]+[/SUP] T cells in COVID-19
Lei He[SUP] #[/SUP][SUP] 1 [/SUP], Quan Zhang[SUP] #[/SUP][SUP] 2 [/SUP], Yue Zhang[SUP] 1 [/SUP], Yixian Fan[SUP] 3 [/SUP], Fahu Yuan[SUP] 4 [/SUP], Songming Li[SUP] 5 [/SUP]
Affiliations
- PMID: 34238338
- DOI: 10.1186/s12964-021-00754-7
Abstract
Background: The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has become an ongoing pandemic. Understanding the respiratory immune microenvironment which is composed of multiple cell types, together with cell communication based on ligand-receptor interactions is important for developing vaccines, probing COVID-19 pathogenesis, and improving pandemic control measures.
Methods: A total of 102 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study. Clinical information, routine laboratory tests, and flow cytometry analysis data with different conditions were collected and assessed for predictive value in COVID-19 patients. Next, we analyzed public single-cell RNA-sequencing (scRNA-seq) data from bronchoalveolar lavage fluid, which offers the closest available view of immune cell heterogeneity as encountered in patients with varying severity of COVID-19. A weighting algorithm was used to calculate ligand-receptor interactions, revealing the communication potentially associated with outcomes across cell types. Finally, serum cytokines including IL6, IL1β, IL10, CXCL10, TNFα, GALECTIN-1, and IGF1 derived from patients were measured.
Results: Of the 102 COVID-19 patients, 42 cases (41.2%) were categorized as severe. Multivariate logistic regression analysis demonstrated that AST, D-dimer, BUN, and WBC were considered as independent risk factors for the severity of COVID-19. T cell numbers including total T cells, CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cells in the severe disease group were significantly lower than those in the moderate disease group. The risk model containing the above mentioned inflammatory damage parameters, and the counts of T cells, with AUROCs ranged from 0.78 to 0.87. To investigate the molecular mechanism at the cellular level, we analyzed the published scRNA-seq data and found that macrophages displayed specific functional diversity after SARS-Cov-2 infection, and the metabolic pathway activities in the identified macrophage subtypes were influenced by hypoxia status. Importantly, we described ligand-receptor interactions that are related to COVID-19 serverity involving macrophages and T cell subsets by communication analysis.
Conclusions: Our study showed that macrophages driving ligand-receptor crosstalk contributed to the reduction and exhaustion of CD8[SUP]+[/SUP] T cells. The identified crucial cytokine panel, including IL6, IL1β, IL10, CXCL10, IGF1, and GALECTIN-1, may offer the selective targets to improve the efficacy of COVID-19 therapy.
Trial registration: This is a retrospective observational study without a trial registration number. Video Abstract.
Keywords: COVID-19; Macrophage; SARS-CoV-2; Single cell RNA-sequencing; T cell.