Human PBMCs Form Lipid Droplets in Response to Spike Proteins
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Updated: Jul 10, 2025
Lipid Droplet Isolation for Quantitative Mass Spectrometry Analysis
Published on: April 17, 2017
Kokilavani Sivaraman1, Paco Pino2, Guillaume Raussin2
1Department of Respiratory Medicine, German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover Medical School, 30625 Hannover, Germany.
Abstract:
Intracellular lipid droplets (LDs) can accumulate in response to inflammation, metabolic stresses, and other physiological/pathological processes. Herein, we investigated whether spike proteins of SARS-CoV-2 induce LDs in human peripheral blood mononuclear cells (PBMCs) and in pulmonary microvascular endothelial cells (HPMECs). PBMCs or HPMECs were incubated alone or with endotoxin-free recombinant variants of trimeric spike glycoproteins (Alpha, Beta, Delta, and Omicron, 12 µg/mL). Afterward, cells were stained with Oil Red O for LDs, cytokine release was determined through ELISA, and the gene expression was analyzed through real-time PCR using TaqMan assays. Our data show that spikes induce LDs in PBMCs but not in HPMECs. In line with this, in PBMCs, spike proteins lower the expression of genes involving lipid metabolism and LD formation, such as SREBF1, HMGCS1, LDLR, and CD36. On the other hand, PBMCs exposed to spikes for 6 or 18 h did not increase in IL-1β, IL-6, IL-8, MCP-1, and TNFα release or expression as compared to non-treated controls. Thus, spike-induced LD formation in PBMCs seems to not be related to cell inflammatory activation. Further detailed studies are warranted to investigate in which specific immune cells spikes induce LDs, and what are the pathophysiological mechanisms and consequences of this induction in vivo.
Insights
SARS-CoV-2 spike proteins induce intracellular lipid droplets (LDs) in human immune cells, but not lung endothelial cells. This LD formation in PBMCs is not linked to increased inflammatory cytokine release.
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.
