The high mortality of COVID-19 is mostly attributed to acute respiratory distress syndrome (ARDS), whose histopathological correlate is diffuse alveolar damage (DAD). Furthermore, severe COVID-19 is often accompanied by a cytokine storm and a disrupted response of the adaptive immune system. Studies aiming to depict this dysregulation have mostly investigated the peripheral cell count as well as the functionality of immune cells. We investigated the impact of SARS-CoV-2 on antigen-presenting cells using multiplexed immunofluorescence. Similar to MERS-CoV and SARS-CoV, SARS-CoV-2 appears to be impairing the maturation of dendritic cells (DCs). DC maturation involves a switch in surface antigen expression, which enables the cells’ homing to lymph nodes and the subsequent activation of T-cells. As quantitative descriptions of the local inflammatory infiltrate are still scarce, we compared the cell population of professional antigen-presenting cells (APC) in the lungs of COVID-19 autopsy cases in different stages of DAD. We found an increased count of myeloid dendritic cells (mDCs) in later stages. Interestingly, mDCs also showed no significant upregulation of maturation markers in DAD-specimens with high viral load. Accumulation of immature mDCs, which are unable to home to lymph nodes, ultimately results in an inadequate T-cell response.
【저자키워드】 COVID-19, SARS-CoV-2, artificial intelligence, dendritic cells, maturation, diffuse alveolar damage (DAD), homing, multiplexed immunofluorescence, 【초록키워드】 ARDS, Cytokine storm, severe COVID-19, SARS-CoV, T-cell Response, T-cells, lung, Local, MERS-CoV, Autopsy, mDCs, Viral load, immune cells, Diffuse alveolar damage, Quantitative, lymph nodes, dendritic cell, acute respiratory distress, marker, Inflammatory, antigen-presenting cell, Lymph node, DAD, dysregulation, Activation, stages, accumulation, syndrome, high mortality, Stage, upregulation, adaptive immune system, description, cell count, cell population, antigen expression, DCs, Cell, subsequent, investigated, appear, histopathological, immature, APC, accompanied, impairing, mDC, 【제목키워드】 Impaired,