Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2
Abstract Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) befor...
Main Authors: | , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Nature Publishing Group
2021-09-01
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Series: | Signal Transduction and Targeted Therapy |
Online Access: | https://doi.org/10.1038/s41392-021-00734-w |
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record_format |
Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2 Signal Transduction and Targeted Therapy |
author_facet |
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 |
author_sort |
Hong-Yi Zheng |
title |
Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2 |
title_short |
Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2 |
title_full |
Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2 |
title_fullStr |
Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2 |
title_full_unstemmed |
Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2 |
title_sort |
pro-inflammatory microenvironment and systemic accumulation of cxcr3+ cell exacerbate lung pathology of old rhesus macaques infected with sars-cov-2 |
publisher |
Nature Publishing Group |
series |
Signal Transduction and Targeted Therapy |
issn |
2059-3635 |
publishDate |
2021-09-01 |
description |
Abstract Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- 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. |
url |
https://doi.org/10.1038/s41392-021-00734-w |
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doaj-f30248b77ef246d48797d06ca6c0e8ac2021-09-05T11:19:11ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352021-09-016111210.1038/s41392-021-00734-wPro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2Hong-Yi Zheng0Xiao-Yan He1Wei Li2Tian-Zhang Song3Jian-Bao Han4Xiang Yang5Feng-Liang Liu6Rong-Hua Luo7Ren-Rong Tian8Xiao-Li Feng9Yu-Hua Ma10Chao Liu11Ming-Hua Li12Yong-Tang Zheng13Key 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 SciencesKey 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 SciencesKey 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 SciencesKey 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 SciencesKunming National High-Level Biosafety Research Center for Non-Human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of SciencesKunming National High-Level Biosafety Research Center for Non-Human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of SciencesKey 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 SciencesKey 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 SciencesKey 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 SciencesKunming National High-Level Biosafety Research Center for Non-Human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of SciencesNational 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 SciencesNational 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 SciencesKunming College of Life Science, University of Chinese Academy of SciencesKey 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 SciencesAbstract Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- 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.https://doi.org/10.1038/s41392-021-00734-w |