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) 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.

• Authors: 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
• Journal: Signal transduction and targeted therapy (Signal Transduct Target Ther) Vol. 6 Issue 1 Pg. 328 (09 01 2021) ISSN: 2059-3635 [Electronic] England
• PMID: 34471088 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Interferon-alpha
• Interleukin-6
• Receptors, CXCR3
• Angiotensin-Converting Enzyme 2

Topics

• Angiotensin-Converting Enzyme 2 (immunology)
• Animals
• CD8-Positive T-Lymphocytes (immunology, pathology)
• COVID-19 (immunology, pathology)
• Cellular Microenvironment (immunology)
• Disease Models, Animal
• Inflammation (immunology, pathology)
• Interferon-alpha (immunology)
• Interleukin-6 (immunology)
• Lung (immunology, pathology, virology)
• Macaca mulatta
• Male
• Receptors, CXCR3 (immunology)
• SARS-CoV-2 (immunology)