Liver, as an immune and detoxification organ, represents an important line of defense against bacteria and
infection and a vulnerable organ that is easily injured during
sepsis.
Artesunate (ART) is an anti-
malaria agent, that also exhibits broad pharmacological activities including anti-inflammatory, immune-regulation and liver protection. In this study, we investigated the cellular responses in liver to
sepsis infection and ART hepatic-protective mechanisms against
sepsis. Cecal
ligation and
puncture (CLP)-induced
sepsis model was established in mice. The mice were administered ART (10 mg/kg, i.p.) at 4 h, and sacrificed at 12 h after the surgery. Liver samples were collected for preparing single-cell
RNA transcriptome sequencing (
scRNA-seq). The
scRNA-seq analysis revealed that
sepsis-induced a dramatic reduction of hepatic endothelial cells, especially the subtypes characterized with proliferation and differentiation. Macrophages were recruited during
sepsis and released inflammatory
cytokines (Tnf, Il1b,
Il6),
chemokines (Ccl6, Cd14), and
transcription factor (Nfkb1), resulting in liver inflammatory responses. Massive apoptosis of lymphocytes and abnormal recruitment of neutrophils caused immune dysfunction. ART treatment significantly improved the survival of CLP mice within 96 h, and partially relieved or reversed the above-mentioned pathological features, mitigating the impact of
sepsis on liver injury,
inflammation, and dysfunction. This study provides comprehensive fundamental proof for the liver protective efficacy of ART against
sepsis infection, which would potentially contribute to its clinical translation for
sepsis therapy. Single cell transcriptome reveals the changes of various hepatocyte subtypes of CLP-induced liver injury and the potential pharmacological effects of
artesunate on
sepsis.