Malaria,a pervasive and devastating disease,is characterized by systemic complications and dysregulated host immune responses to Plasmodium infection.Artemisinin derivatives,particularly artesunate(ART),are a cornerst...Malaria,a pervasive and devastating disease,is characterized by systemic complications and dysregulated host immune responses to Plasmodium infection.Artemisinin derivatives,particularly artesunate(ART),are a cornerstone in malaria treatment strategies.Although the precise immunomodulatory mechanisms remain unclear,ART not only kills parasites but also impacts host immune homeostasis.In this study,we employed single-cell RNA sequencing to characterize the cellular landscape of 241,837 cells from multiple murine tissues(including liver,spleen,and peripheral blood)upon Plasmodium berghei ANKA(PbA)infection and after ART treatment.Meanwhile,we observed significant transcriptomic shifts across diverse immune cell types,with the liver exhibiting the most pronounced changes in response to PbA infection.Notably,CD8^(+)GZMB^(+)T lymphocytes,characterized by elevated cytokine and cytotoxic module scores,play a pivotal role in driving hepatic injury.Furthermore,ART modulated this pathogenic subtype via the JAK2-STAT3 pathway,reducing its frequency and mitigating its inflammatory response.Our research provides a valuable dataset resource for exploring malaria immunopathogenesis and elucidates a novel immunoregulatory mechanism of ART within the infected host.展开更多
基金financial support from the National Natural Science Foundation of China(82521104,82274182,82441001)the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2023D003,CI2023E005TS05)+6 种基金the CACMS Innovation Fund(CI2023E002,ZG2024001-05)the National Key Research and Development Program of China(2020YFA0908000)the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research(2020YFE0205100)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(no.ZYYZDXK-2023230)the Shenzhen Medical Research Funds(B2302051)the Distinguished Expert Project of Sichuan Province Tianfu Scholar(CW202002)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ13-ZD-07,ZZ18-ND-10,ZZ17-ND-10,ZZ15-ND-10,ZZ14-ND-010,ZZ14-FL-010,ZZ14-YQ-050)。
文摘Malaria,a pervasive and devastating disease,is characterized by systemic complications and dysregulated host immune responses to Plasmodium infection.Artemisinin derivatives,particularly artesunate(ART),are a cornerstone in malaria treatment strategies.Although the precise immunomodulatory mechanisms remain unclear,ART not only kills parasites but also impacts host immune homeostasis.In this study,we employed single-cell RNA sequencing to characterize the cellular landscape of 241,837 cells from multiple murine tissues(including liver,spleen,and peripheral blood)upon Plasmodium berghei ANKA(PbA)infection and after ART treatment.Meanwhile,we observed significant transcriptomic shifts across diverse immune cell types,with the liver exhibiting the most pronounced changes in response to PbA infection.Notably,CD8^(+)GZMB^(+)T lymphocytes,characterized by elevated cytokine and cytotoxic module scores,play a pivotal role in driving hepatic injury.Furthermore,ART modulated this pathogenic subtype via the JAK2-STAT3 pathway,reducing its frequency and mitigating its inflammatory response.Our research provides a valuable dataset resource for exploring malaria immunopathogenesis and elucidates a novel immunoregulatory mechanism of ART within the infected host.
