Your browser doesn't support javascript.
In silico immune infiltration profiling combined with functional enrichment analysis reveals a potential role for naïve B cells as a trigger for severe immune responses in the lungs of COVID-19 patients.
Wu, Yi-Ying; Wang, Sheng-Huei; Wu, Chih-Hsien; Yen, Li-Chen; Lai, Hsing-Fan; Ho, Ching-Liang; Chiu, Yi-Lin.
  • Wu YY; Division of Hematology and Oncology Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (R.O.C.).
  • Wang SH; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (R.O.C.).
  • Wu CH; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan (R.O.C.).
  • Yen LC; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan (R.O.C.).
  • Lai HF; Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan (R.O.C.).
  • Ho CL; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan (R.O.C.).
  • Chiu YL; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan (R.O.C.).
PLoS One ; 15(12): e0242900, 2020.
Article in English | MEDLINE | ID: covidwho-953000
ABSTRACT
COVID-19, caused by SARS-CoV-2, has rapidly spread to more than 160 countries worldwide since 2020. Despite tremendous efforts and resources spent worldwide trying to explore antiviral drugs, there is still no effective clinical treatment for COVID-19 to date. Approximately 15% of COVID-19 cases progress to pneumonia, and patients with severe pneumonia may die from acute respiratory distress syndrome (ARDS). It is believed that pulmonary fibrosis from SARS-CoV-2 infection further leads to ARDS, often resulting in irreversible impairment of lung function. If the mechanisms by which SARS-CoV-2 infection primarily causes an immune response or immune cell infiltration can be identified, it may be possible to mitigate excessive immune responses by modulating the infiltration and activation of specific targets, thereby reducing or preventing severe lung damage. However, the extent to which immune cell subsets are significantly altered in the lung tissues of COVID-19 patients remains to be elucidated. This study applied the CIBERSORT-X method to comprehensively evaluate the transcriptional estimated immune infiltration landscape in the lung tissues of COVID-19 patients and further compare it with the lung tissues of patients with idiopathic pulmonary fibrosis (IPF). We found a variety of immune cell subtypes in the COVID-19 group, especially naïve B cells were highly infiltrated. Comparison of functional transcriptomic analyses revealed that non-differentiated naïve B cells may be the main cause of the over-active humoral immune response. Using several publicly available single-cell RNA sequencing data to validate the genetic differences in B-cell populations, it was found that the B-cells collected from COVID-19 patients were inclined towards naïve B-cells, whereas those collected from IPF patients were inclined towards memory B-cells. Further differentiation of B cells between COVID-19 mild and severe patients showed that B cells from severe patients tended to be antibody-secreting cells, and gene expression showed that B cells from severe patients were similar to DN2 B cells that trigger extrafollicular response. Moreover, a higher percentage of B-cell infiltration seems associated with poorer clinical outcome. Finally, a comparison of several specific COVID-19 cases treated with targeted B-cell therapy suggests that appropriate suppression of naïve B cells might potentially be a novel strategy to alleviate the severe symptoms of COVID-19.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Computer Simulation / B-Lymphocytes / COVID-19 / Lung Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2020 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Computer Simulation / B-Lymphocytes / COVID-19 / Lung Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2020 Document Type: Article