Single Cell Transcriptomic Re-analysis of Immune Cells in Bronchoalveolar Lavage Fluids Reveals the Correlation of B Cell Characteristics and Disease Severity of Patients with SARS-CoV-2 Infection
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
The coronavirus disease 2019 (COVID-19) pandemic (severe acute respiratory syndrome coronavirus 2) is a global infectious disease with rapid spread. Some patients have severe symptoms and clinical signs caused by an excessive inflammatory response, which increases the risk of mortality. In this study, we reanalyzed scRNA-seq data of cells from bronchoalveolar lavage fluids of patients with COVID-19 with mild and severe symptoms, focusing on Ab-producing cells. In patients with severe disease, B cells seemed to be more activated and expressed more immunoglobulin genes compared with cells from patients with mild disease, and macrophages expressed higher levels of the TNF superfamily member B-cell activating factor but not of APRIL (a proliferation-inducing ligand). In addition, macrophages from patients with severe disease had increased pro-inflammatory features and pathways associated with Fc receptor-mediated signaling, compared with patients with mild disease. CCR2-positive plasma cells accumulated in patients with severe disease, probably because of increased CCL2 expression on macrophages from patients with severe disease. Together, these results support the hypothesis that different characteristics of B cells might be associated with the severity of COVID-19 infection.
Abstract
The coronavirus disease 2019 (COVID-19) pandemic (severe acute respiratory syndrome coronavirus 2) is a global infectious disease with rapid spread. Some patients have severe symptoms and clinical signs caused by an excessive inflammatory response, which increases the risk of mortality. In this study, we reanalyzed scRNA-seq data of cells from bronchoalveolar lavage fluids of patients with COVID-19 with mild and severe symptoms, focusing on Ab-producing cells. In patients with severe disease, B cells seemed to be more activated and expressed more immunoglobulin genes compared with cells from patients with mild disease, and macrophages expressed higher levels of the TNF superfamily member B-cell activating factor but not of APRIL (a proliferation-inducing ligand). In addition, macrophages from patients with severe disease had increased pro-inflammatory features and pathways associated with Fc receptor-mediated signaling, compared with patients with mild disease. CCR2-positive plasma cells accumulated in patients with severe disease, probably because of increased CCL2 expression on macrophages from patients with severe disease. Together, these results support the hypothesis that different characteristics of B cells might be associated with the severity of COVID-19 infection.
참고문헌 (34)
- Zhao J, "Antibody responses to SARSCoV-2 in patients of novel coronavirus disease 2019", Clin Infect Dis, 71, pp.2027~2034 (2020)
- Coronavirus disease (COVID-19) situation, "World Health Organization", World Health Organization, ~, pp.report-154 (2020)
- Mehta P, "COVID-19: consider cytokine storm syndromes and immunosuppression", Lancet, 395, pp.1033~1034 (2020)
- Lee JS, "Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19", Sci Immunol, 5, pp.eabd1554~ (2020)
- Liao M, "Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19", Nat Med, 26, pp.842~844 (2020)
- Arunachalam PS, "Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans", Science, 369, pp.1210~1220 (2020)
- Chua RL, "COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis", Nat Biotechnol, 38, pp.970~979 (2020)
- Jiang S, "Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses", Trends Immunol, 41, pp.355~359 (2020)
- Ni L, "Detection of sars-cov-2-specific humoral and cellular immunity in covid-19 convalescent individuals", Immunity, 52, pp.971~977 (2020)
- Vabret N, "Immunology of COVID-19 : current state of the science", Immunity, 52, pp.910~941 (2020)
- Grifoni A, "Targets of t cell responses to sars-cov-2 coronavirus in humans with COVID-19 disease and unexposed individuals", Cell, 181, pp.1489.e15~1501.e15 (2020)
- Schultheiß C, "Next-generation sequencing of t and b cell receptor repertoires from COVID-19patients showed signatures associated with severity of disease", Immunity, 53, pp.442.e4~455.e4 (2020)
- Okba NMA, "Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease patients", Emerg Infect Dis, 26, pp.1478~1488 (2020)
- Oh JE, "Migrant memory B cells secrete luminal antibody in the vagina", Nature, 571, pp.122~126 (2019)
- Henneken M, "Differential expression of chemokine receptors on peripheral blood B cells from patients with rheumatoid arthritis and systemic lupus erythematosus", Arthritis Res Ther, 7, pp.R1001~R1013 (2005)
- Stavnezer J, "IgH chain class switch recombination : mechanism and regulation", J Immunol, 193, pp.5370~5378 (2014)
- Zimmermann M, "Antigen extraction and b cell activation enable identification of rare membrane antigen specific human b cells", Front Immunol, 10, pp.829~ (2019)
- Huo L, "Isolation and characterization of murine fra-1 : induction mediated by CD40 and surface Ig is protein kinase C dependent", J Immunol, 157, pp.3812~3818 (1996)
- Vincent FB, "The BAFF", APRIL system in SLE pathogenesis, 2014, pp.10, 365~373
- Sakai J, "The role of baff system molecules in host response to pathogens", Clin Microbiol Rev, 30, pp.991~1014 (2017)
- Mackay F, "Cracking the BAFF code", Nat Rev Immunol, 9, pp.491~502 (2009)
- Yang M, "B cell maturation antigen, the receptor for a proliferation-inducing ligand and B cell-activating factor of the TNF family, induces antigen presentation in B cells", J Immunol, 175, pp.2814~2824 (2005)
- Ye Q, "The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19", J Infect, 80, pp.607~613 (2020)
- Nakayama T, "Cutting edge : profile of chemokine receptor expression on human plasma cells accounts for their efficient recruitment to target tissues", J Immunol, 170, pp.1136~1140 (2003)
- Al Rayes MH, "The bone marrow microenvironment influences the differential chemokine receptor expression of normal and neoplastic plasma cells", Blood, 105, pp.4895~4896 (2005)
- Wen W, "Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing", Cell Discov, 6, pp.31~ (2020)
- Dillon SR, "B-lymphocyte stimulator", a proliferation-inducing ligand heterotrimers are elevated in the sera of patients with autoimmune disease and are neutralized by atacicept and B-cell maturation antigen-immunoglobulin, 2010, pp.12, R48~
- Hua C, "A proliferation inducing ligand(APRIL)promotes IL-10 production and regulatory functions of human B cells", J Autoimmun, 73, pp.64~72 (2016)
- Zhang L, "Antibody responses against SARS coronavirus are correlated with disease outcome of infected individuals", J Med Virol, 78, pp.1~8 (2006)
- Iwasaki A, "The potential danger of suboptimal antibody responses in COVID-19", Nat Rev Immunol, 20, pp.339~341 (2020)
- Ghisolfi S, "Predicted COVID-19 fatality rates based on age, sex, comorbidities and health system capacity", BMJ Glob Health, 5, pp.e003094~ (2020)
- Zheng Y, "A human circulating immune cell landscape in aging and COVID-19", Protein Cell, 11, pp.740~770 (2020)
- Wong LS, "Age-related differences in immunological responses to sars-cov-2", J Allergy Clin Immunol Pract, 8, pp.3251~3258 (2020)
- "Afucosylated immunoglobulin G responses are a hallmark of enveloped virus infections and show an exacerbated phenotype in COVID-19"[URL]
