Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis
10.1016/j.jpha.2023.02.006
- Author:
Jiayun CHEN
1
;
Xueling HE
;
Yunmeng BAI
;
Jing LIU
;
Kwan-Yin WONG
;
Lulin XIE
;
Qian ZHANG
;
Piao LUO
;
Peng GAO
;
Liwei GU
;
Qiuyan GUO
;
Guangqing CHENG
;
Chen WANG
;
Jigang WANG
Author Information
1. State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs,Artemisinin Research Center,and Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing,100700,China;Department of Nephrology,Shenzhen Key Laboratory of Kidney Diseases,and Shenzhen Clinical Research Centre for Geriatrics,Shenzhen People's Hospital,The First Affiliated Hospital,Southern Uni
- Keywords:
Artesunate;
Sepsis;
Single-cell RNA sequencing;
Immunomodulatory activity
- From:
Journal of Pharmaceutical Analysis
2023;13(7):817-829
- CountryChina
- Language:Chinese
-
Abstract:
Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomod-ulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various im-mune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils'chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.
