摘要
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 immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune 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.
基金
support by the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research,China(Grant No.:2020YFE0205100)
the National Key Research and Development Program of China(Grant Nos.:2020YFA0908000,2022YFC2303600)
the Distinguished Expert Project of Sichuan Province Tianfu Scholar(Grant No.:CW202002)
the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine,China(Grant No.:ZYYCXTD-C-202002)
the National Natural Science Foundation of China(Grant Nos.:82141001,82274182,82074098,82173914)
the China Academy of Chinese Medical Sciences(CACMS)Innovation Fund,China(Grant Nos.:CI2021A05101,CI2021A05104)
the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(Grant No.:CI2021B014)
the Science and Technology Foundation of Shenzhen,China(Grant No.:JCYJ20210324115800001)
the Science and Technology Foundation of Shenzhen,China(Shenzhen Clinical Medical Research Center for Geriatric Diseases),the National Key R&D Program of China Key Projects for International Cooperation on Science,Technology and Innovation(Grant No.:2020YFE0205100)
the Fundamental Research Funds for the Central Public Welfare Research Institutes,China(Grant Nos.:ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-YQ-052,ZZ14-FL-002,ZZ14-ND-010,ZZ15-ND-10),Shenzhen Governmental Sustainable Development Fund,China(Grant No.:KCXFZ20201221173612034)
Shenzhen key Laboratory of Kidney Diseases,China(Grant No.:ZDSYS201504301616234)
Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties,China(Grant No.:SZGSP001).
