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.
【저자키워드】 Infectious diseases, Infection, 【초록키워드】 COVID-19, Treatment, coronavirus disease, SARS-CoV-2, Apoptosis, Coronavirus disease 2019, coronavirus, severe COVID-19, IL-6, SARS-COV-2 infection, interferon, lung, animal model, immunopathology, severe acute respiratory syndrome Coronavirus, angiotensin-converting enzyme 2, autophagy, interleukin 6, Peripheral blood, T cell, interleukin, FFPE, cells, Lungs, understanding, respiratory, Chemokine receptor, rhesus macaques, NF-κB, rhesus macaque, Angiotensin-converting enzyme, Analysis, angiotensin, IFN-α, both lungs, formalin, Quantitative analysis, acute respiratory syndrome, Activation, acute respiratory syndrome coronavirus, tissue, acute respiratory syndrome coronavirus 2, lung tissue, protein expression, CXCR3, staining, CD8+ cells, formalin-fixed paraffin-embedded, paraffin, motif, microenvironment, multiplex immunofluorescence, nuclear, pro-inflammatory, feature, Cell, T-box, significantly, elevated, changes in, demonstrated, correlated, immunopathological, CD8+ cell, 【제목키워드】 Lung pathology, rhesus macaque, microenvironment, Cell, exacerbate, infected with SARS-CoV-2,