tetano
Editor, Senior Moderator
Signal Transduct Target Ther
. 2021 Sep 1;6(1):328.
doi: 10.1038/s41392-021-00734-w.
Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2
Hong-Yi Zheng[SUP] #[/SUP][SUP] 1 [/SUP], Xiao-Yan He[SUP] #[/SUP][SUP] 1 2 [/SUP], Wei Li[SUP] #[/SUP][SUP] 1 2 [/SUP], Tian-Zhang Song[SUP] 1 [/SUP], Jian-Bao Han[SUP] 3 [/SUP], Xiang Yang[SUP] 3 [/SUP], Feng-Liang Liu[SUP] 1 [/SUP], Rong-Hua Luo[SUP] 1 [/SUP], Ren-Rong Tian[SUP] 1 [/SUP], Xiao-Li Feng[SUP] 3 [/SUP], Yu-Hua Ma[SUP] 4 [/SUP], Chao Liu[SUP] 4 [/SUP], Ming-Hua Li[SUP] 2 [/SUP], Yong-Tang Zheng[SUP] 5 6 7 8 9 [/SUP]
Affiliations
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.
. 2021 Sep 1;6(1):328.
doi: 10.1038/s41392-021-00734-w.
Pro-inflammatory microenvironment and systemic accumulation of CXCR3+ cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2
Hong-Yi Zheng[SUP] #[/SUP][SUP] 1 [/SUP], Xiao-Yan He[SUP] #[/SUP][SUP] 1 2 [/SUP], Wei Li[SUP] #[/SUP][SUP] 1 2 [/SUP], Tian-Zhang Song[SUP] 1 [/SUP], Jian-Bao Han[SUP] 3 [/SUP], Xiang Yang[SUP] 3 [/SUP], Feng-Liang Liu[SUP] 1 [/SUP], Rong-Hua Luo[SUP] 1 [/SUP], Ren-Rong Tian[SUP] 1 [/SUP], Xiao-Li Feng[SUP] 3 [/SUP], Yu-Hua Ma[SUP] 4 [/SUP], Chao Liu[SUP] 4 [/SUP], Ming-Hua Li[SUP] 2 [/SUP], Yong-Tang Zheng[SUP] 5 6 7 8 9 [/SUP]
Affiliations
- PMID: 34471088
- DOI: 10.1038/s41392-021-00734-w
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.