Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infe...Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000single-nucleus transcriptomes of the lung, liver,kidney, and cerebral cortex in rhesus macaques(Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multiorgan dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019(COVID-19).Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway,which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy(an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection,which may facilitate the development of therapeutic interventions for COVID-19.展开更多
Mucosal vaccines have risen to prominence in the corona virus disease 2019(COVID-19)pandemic due to their ability to elicit both local antibody and tissue-resident T cell responses,affording a dual-layered defense aga...Mucosal vaccines have risen to prominence in the corona virus disease 2019(COVID-19)pandemic due to their ability to elicit both local antibody and tissue-resident T cell responses,affording a dual-layered defense against infection and transmission at respiratory entry sites.While intramuscular vaccines predominantly focus on systemic immunity,mucosal vaccines offer a more nuanced,site-specific approach.However,the field faces a dearth of mucosal vaccine options for respiratory diseases,starkly contrasting to the extensive array of well-characterized injectable vaccines.The unique features of mucosal surfaces necessitate specialized adjuvants and delivery systems,adding complexity to adapting injectable vaccine technologies for mucosal applications.Here,we review the recent insights into the specificities of respiratory mucosal immunology that provide a foundation for future innovations besides the emerging vaccine platforms,newly discovered adjuvants,and vaccine delivery systems,which may open promising avenues for developing mucosal vaccines targeting respiratory pathogens.展开更多
基金supported by the National Basic Research Program of China(2020YFA0804000,2020YFC0842000,2020YFA0112200,2021YFC2301703)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32010100)+6 种基金Special Associate Research Program of the Chinese Academy of Sciences(E1290601)National Natural Science Foundation of China(32122037,81891001,32192411,32100512,U1902215)Collaborative Research Fund of the Chinese Institute for Brain Research,Beijing(2020-NKX-PT-03)CAS Project for Young Scientists in Basic Research(YSBR-013)Young Elite Scientist Sponsorship Program by the China Association for Science and Technology(2020QNRC001)National Resource Center for Non-Human Primates。
文摘Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000single-nucleus transcriptomes of the lung, liver,kidney, and cerebral cortex in rhesus macaques(Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multiorgan dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019(COVID-19).Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway,which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy(an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection,which may facilitate the development of therapeutic interventions for COVID-19.
基金funded by the Emergency Key Program of Guangzhou Laboratory (grant No.EKPG21-21 to Hua Peng).
文摘Mucosal vaccines have risen to prominence in the corona virus disease 2019(COVID-19)pandemic due to their ability to elicit both local antibody and tissue-resident T cell responses,affording a dual-layered defense against infection and transmission at respiratory entry sites.While intramuscular vaccines predominantly focus on systemic immunity,mucosal vaccines offer a more nuanced,site-specific approach.However,the field faces a dearth of mucosal vaccine options for respiratory diseases,starkly contrasting to the extensive array of well-characterized injectable vaccines.The unique features of mucosal surfaces necessitate specialized adjuvants and delivery systems,adding complexity to adapting injectable vaccine technologies for mucosal applications.Here,we review the recent insights into the specificities of respiratory mucosal immunology that provide a foundation for future innovations besides the emerging vaccine platforms,newly discovered adjuvants,and vaccine delivery systems,which may open promising avenues for developing mucosal vaccines targeting respiratory pathogens.
