Pro-inflammatory microenvironment and systemic accumulation of CXCR3+cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2  

作　　者：Hong-Yi Zheng Xiao-Yan He Wei Li Tian-Zhang Song Jian-Bao Han Xiang Yang Feng-Liang Liu Rong-Hua Luo Ren-Rong Tian Xiao-Li Feng Yu-Hua Ma Chao Liu Ming-Hua Li Yong-Tang Zheng 

机构地区：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences,KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan,China [2]Kunming College of Life Science,University of Chinese Academy of Sciences,Kunming,Yunnan,China [3]Kunming National High-Level Biosafety Research Center for Non-Human Primates,Center for Biosafety Mega-Science,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan,China [4]National Resource Center for Non-Human Primates,National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility),Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan,China [5]Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory),Guangzhou,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第10期3033-3044,共12页信号转导与靶向治疗（英文）

基　　金：supported by the National Key Research and Development Program of China(2020YFC0842000,2020YFC0847000).

摘　　要：Understanding the pathological features of severe acute respiratory syn drome coronavirus 2(SARS-CoV-2)infect io n in an animal model is crucial for the treatment of coronavirus disease 2019(COVID-19).Here,we compared imnnunopathological changes in young and old rhesus macaques(RMs)before and after SARS-CoV-2 infection at the tissue level.Quantitative analysis of multiplex immunofluoresce nee staining images of formali n-fixed paraffi n-embedded(FFPE)sections showed that SARS-CoV-2 infectio n specifically induced elevated levels of apoptosis,autophagy,and nuclear factor kappa-B(NF-kB)activation of angiotensirv convert!ng enzyme 2(ACE2)+cells,and increased interferon a(IFN-a)-and interleukin 6(IL-6)-secreting cells and C-X-C motif chemokine receptor 3(CXCR3)+cells in lung tissue of old RMs.This pathological pattern,which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens,was significantly correlated with the systemic accumulation of CXCR3+cells in lungs,spleens,and peripheral blood.Furthermore,the ratio of CXCR3+to T-box protein expression in T cell(T-bet)+(CXCR3+/T-bet+ratio)in CD8+cells may be used as a predictor of severe COVID-19.These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+cells in predicting severe COVID-19.

关 键 词：CXCR3 SPLEEN lung 

分 类 号：R373[医药卫生—病原生物学]