Investigating the Intercellular Communication Network of Immune Cell in Acute Respiratory Distress Syndrome with Sepsis.

Pei Tao,Yinghong Fan,Wei Zeng,Jinzhou He,Tao Ai,Liang Cheng

doi:10.1155/2022/4586648

Abstract

Acute respiratory distress syndrome (ARDS) is recognized as a serious public health issue that results in respiratory failure and high mortality rates. The syndrome is characterized by immune cell aggregation, communication, activation, and alveolar epithelial damage. To elucidate the complex dynamic process of the immune system's response in ARDS, we construct the intercellular communication network of immune cells in ARDS based on a single-cell RNA sequencing dataset (including three sepsis-induced ARDS patients and four sepsis-only patients). The results show that macrophages relayed most of the intercellular signals (ligand–receptor pairs) in both groups. Many genes related to immune response (IFI44L, ISG, and HLA-DQB1) and biological functions (response to virus, negative regulation of viral life cycle, and response to interferon-beta) were detected via differentially expressed gene analysis of macrophages between the two groups. Deep analysis of the intercellular signals related to the macrophage found that sepsis-induced ARDS harbored distinctive intercellular signals related to chemokine–chemokine receptors (CCL3/4/5−CCR1), which mainly are involved in the disturbance of the STAT family transcription factors (TFs), such as STAT2 and STAT3. These signals and downstream TFs might play key roles in macrophage M1/M2 polarization in the process of sepsis-induced ARDS. This study provides a comprehensive view of the intercellular communication landscape between sepsis and sepsis-induced ARDS and identifies key intercellular communications and TFs involved in sepsis-induced ARDS. We believe that our study provides valuable clues for understanding the immune response mechanisms of ARDS.

Highlights

Acute respiratory distress syndrome (ARDS) is the most severe form of acute lung injury, comprising up to 10% of intensive care unit admissions [1]
We believe that our study provides valuable clues for understanding the immune response mechanisms of ARDS
Intercellular signaling among different immune cell types was analyzed by CellCall, and macrophages exhibited extensive communication with other immune cells (Figure 1(d))

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is the most severe form of acute lung injury, comprising up to 10% of intensive care unit admissions [1]. Sepsis is a critical infectious condition that can cause immune system responses and organ dysfunction [5]. Severe sepsis is known to cause fatal stages of disease development that involve lactic acidosis, oliguria, and ARDS [6]. Many studies have attempted to elucidate how ARDS occurs, such as explaining how pulmonary edema fluid accumulates due to lung inflammation and increased alveolar endothelial and epithelial permeabilities [7,8,9]. Researchers have not yet elucidated the multifactorial mechanisms by which sepsis induces ARDS, nor have they distinguished the mechanism of sepsis and sepsis-induced ARDS, which could further explain how and why ARDS occur

Results

Discussion

Conclusion