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
,
2
;
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
2. 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.
