4.7 Article

Single-cell RNA sequencing reveals the sustained immune cell dysfunction in the pathogenesis of sepsis secondary to bacterial pneumonia

Journal

GENOMICS
Volume 113, Issue 1, Pages 1219-1233

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2021.01.026

Keywords

Single cell transcriptomics; Sepsis; Immune cells

Funding

  1. National Science and Technology Major Project of China [2017ZX10202202]
  2. Guangzhou Science and Technology Plan Project [201804020001]
  3. Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program [2017BT01S131]
  4. National Natural Science Foundation of China [32070833, 81873926]
  5. Key-Area Research and Development Program of Guangdong Province, Modernization of Chinese medicine in Lingnan [2020B1111100011]

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This study used single cell RNA sequencing to analyze the quantity and function of immune cells in patients with sepsis secondary to bacterial pneumonia. The findings showed upregulation of interferon gamma response, activation and exhaustion of T/NK cell subtypes, and increased proportion of plasma cells during the disease course. These alterations may be associated with the occurrence and development of the disease.
Sepsis is a leading cause of mortality in intensive care unit worldwide, it's accompanied by immune cell dysfunction induced by multiple factors. However, little is known about the specific alterations in immune cells in the dynamic pathogenesis of sepsis secondary to bacterial pneumonia. Here, we used single cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) in a healthy control and two patients with sepsis secondary to bacterial pneumonia, including acute, stable and recovery stage. We analyzed the quantity and function of immune cells. During disease course, interferon gamma response was upregulated; T/NK cell subtypes presented activation and exhaustion properties, which might be driven by monocytes through IL-1 beta signaling pathways; The proportion of plasma cells was increased, which might be driven by NK cells through IFN signaling pathways; Additionally, interferon gamma response was upregulated to a greater degree in sepsis secondary to pneumonia induced by SARS-COV-2 compared with that induced by influenza virus and bacteria.

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