A collaborative study conducted by researchers from Hannover Medical School in Germany, ExcellGene SA in Switzerland, and École Polytechnique Fédérale de Lausanne in Switzerland has shed light on the impact of SARS-CoV-2 spike proteins on human peripheral blood mononuclear cells (PBMCs). The study aimed to investigate the formation of lipid droplets (LDs) in PBMCs and pulmonary microvascular endothelial cells (HPMECs) in response to spike proteins and its potential implications.
The researchers exposed PBMCs and HPMECs to different variants of spike glycoproteins from SARS-CoV-2. They discovered that spike proteins induced the formation of LDs in PBMCs but not in HPMECs. Interestingly, the size and distribution of LDs varied depending on the spike protein variant. For instance, the “Omicron” variant induced larger LDs in larger cells, while the “Beta” variant had a lower effect on LD formation.
To delve deeper into the molecular mechanisms at play, the researchers analyzed the gene expression of key players in lipid metabolism and LD formation. They found that spike proteins decreased the expression of genes associated with lipid metabolism and LD formation, indicating interference with lipid metabolism pathways.
Furthermore, the study observed that spike-induced LD formation occurred even under conditions of lipid deprivation, raising questions about the underlying mechanisms and the potential significance of ACE2 receptor translocation in immune cells.
It is worth noting that spike proteins did not increase the production or expression of pro-inflammatory cytokines or chemokines in PBMCs. This suggests that LD formation in PBMCs is not solely driven by elevated cytokine or chemokine production.
In contrast to PBMCs, spike proteins did not induce LD formation in HPMECs, aligning with previous findings of low levels of the ACE2 receptor in these cells. This suggests that the presence of ACE2 in spike-induced LD formation might be a contributing factor.
In summary, this study provides crucial insights into the interaction between SARS-CoV-2 spike proteins and human PBMCs. The induction of LDs in PBMCs, even under lipid-deprived conditions, raises intriguing questions about the potential role of LDs in cellular stress responses. The observed reduction in the expression of genes related to lipid metabolism and LD formation suggests interference with lipid metabolism pathways. Further research is needed to fully understand the complex relationship between spike proteins and cellular lipid homeostasis.
Understanding the mechanisms and consequences of spike-induced LD formation in immune cells is crucial for advancing our knowledge of COVID-19 pathophysiology and may lead to new therapeutic approaches. As the pandemic continues, research like this remains essential for unraveling the mysteries of the virus and its effects on the human body.