Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2.
Hong-Yi ZhengXiao-Yan HeWei LiTian-Zhang SongJian-Bao HanXiang YangFeng-Liang LiuRong-Hua LuoRen-Rong TianXiao-Li FengYu-Hua MaChao LiuMing-Hua LiYong-Tang ZhengPublished in: Signal transduction and targeted therapy (2021)
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.
Keyphrases
- respiratory syndrome coronavirus
- sars cov
- induced apoptosis
- cell cycle arrest
- coronavirus disease
- endoplasmic reticulum stress
- cell death
- signaling pathway
- stem cells
- pi k akt
- peripheral blood
- early onset
- immune response
- high resolution
- toll like receptor
- cell proliferation
- mesenchymal stem cells
- high glucose
- diabetic rats
- endothelial cells
- bone marrow
- combination therapy
- mass spectrometry