Impaired Dendritic Cell Homing in COVID-19

Abstract

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.

Advances in understanding epigenetic impacts on dendritic cell regulation and function

“…Other studies have also shown DC deficits, reduced potential for stimulating naïve CD4+ T cells, upregulation of proinflammatory markers, increased proliferative response and delayed regeneration in COVID‐19 patients 63 . Lung tissue autopsies of COVID‐19 patients revealed impaired DC maturation or homing, mDC accumulation, and decreased migration to lymph nodes leading to deficient T‐cell response 64 . Hence, DCs continue to be in focus for COVID‐19 research, 65–74 and clinical trials e.g.…”

“…63 Lung tissue autopsies of COVID-19 patients revealed impaired DC maturation or homing, mDC accumulation, and decreased migration to lymph nodes leading to deficient T-cell response. 64 Hence, DCs continue to be in focus for COVID-19 research, [65][66][67][68][69][70][71][72][73][74] and clinical trials e.g. NCT04685603, NCT04816760 and NCT04523246.…”

Immune Cells in Subretinal Wound Healing and Fibrosis

“…Ahadome et al (2016) showed that classical DC contributed to ocular mucosal fibrosis through the retinoic acid pathway in a model of allergic eye disease. Impaired DC maturation can lead to inadequate T-cell response and contribute to organ fibrosis as observed in COVID-19 patients (Borcherding et al, 2021). It has been reported that DCs contribute to scar formation in liver fibrosis and multiple sclerosis directly through secreting metalloproteinase and their inhibitors (Rahman and Aloman, 2013).…”

Mechanisms of Cardiovascular System Injury Induced by COVID-19 in Elderly Patients With Cardiovascular History

“…However, COVID-19 infection is characterized by lymphopenia ( 37 ). Probably, SARS-CoV-2 exerts immune evasion through impaired maturation of dendritic cells, leading to hampered dendritic cells (DCs) homing to lymph nodes and failure of T lymphocytes activation ( 38 ).…”