Human PBMCs Form Lipid Droplets in Response to Spike Proteins

Area of Science:

• Cell Biology
• Immunology
• Virology

Background:

• Intracellular lipid droplets (LDs) are dynamic organelles involved in lipid storage and metabolism.
• LD accumulation is observed in various physiological and pathological conditions, including inflammation and metabolic stress.
• The SARS-CoV-2 spike protein's role in cellular lipid metabolism remains incompletely understood.

Purpose of the Study:

• To investigate the effect of SARS-CoV-2 spike proteins on LD formation in human peripheral blood mononuclear cells (PBMCs) and pulmonary microvascular endothelial cells (HPMECs).
• To examine the impact of spike proteins on lipid metabolism gene expression and cytokine release in these cell types.

Main Methods:

• Human PBMCs and HPMECs were incubated with recombinant SARS-CoV-2 spike variants (Alpha, Beta, Delta, Omicron).
• Lipid droplets were visualized using Oil Red O staining.
• Cytokine release was quantified via ELISA, and gene expression of lipid metabolism-related genes was analyzed using real-time PCR.

Main Results:

• SARS-CoV-2 spike proteins induced LD formation in PBMCs, but not in HPMECs.
• Spike protein exposure led to decreased expression of key genes involved in lipid metabolism and LD formation (SREBF1, HMGCS1, LDLR, CD36) in PBMCs.
• No significant increase in the release or expression of inflammatory cytokines (IL-1β, IL-6, IL-8, MCP-1, TNFα) was observed in spike-treated PBMCs.

Conclusions:

• SARS-CoV-2 spike proteins induce LD formation in human PBMCs, suggesting a role in immune cell lipid homeostasis.
• Spike-induced LDs in PBMCs appear independent of inflammatory activation.
• Further research is needed to elucidate the specific immune cell types involved and the in vivo pathophysiological consequences of spike-induced LD formation.