Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

Human PBMCs Form Lipid Droplets in Response to Spike Proteins

Kokilavani Sivaraman
,
Paco Pino
ORCID logo ,
Guillaume Raussin
,
Stephanie Anchisi
,
Charles Metayer
,
Nicolas Dagany
,
Julia Held
,
Sabine Wrenger
ORCID logo ,
Tobias Welte
,
Maria J Wurm
,
Florian M Wurm
,
Beata Olejnicka
ORCID logo ,
Sabina Janciauskiene
*
Version 1 : Received: 22 July 2023 / Approved: 24 July 2023 / Online: 25 July 2023 (08:14:12 CEST)

A peer-reviewed article of this Preprint also exists.

Sivaraman, K.; Pino, P.; Raussin, G.; Anchisi, S.; Metayer, C.; Dagany, N.; Held, J.; Wrenger, S.; Welte, T.; Wurm, M.J.; Wurm, F.M.; Olejnicka, B.; Janciauskiene, S. Human PBMCs Form Lipid Droplets in Response to Spike Proteins. Microorganisms 2023, 11, 2683. Sivaraman, K.; Pino, P.; Raussin, G.; Anchisi, S.; Metayer, C.; Dagany, N.; Held, J.; Wrenger, S.; Welte, T.; Wurm, M.J.; Wurm, F.M.; Olejnicka, B.; Janciauskiene, S. Human PBMCs Form Lipid Droplets in Response to Spike Proteins. Microorganisms 2023, 11, 2683.

Abstract

Intracellular lipid droplets (LDs) can occur 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 (HPMEC). PBMCs or HPMEC were incubated alone or with endotoxin-free recombinant variants of trimeric spike glycoproteins (Alpha, Beta, Delta, and Omicron, 12 µg/ml). Afterwards, cells were stained with Oil Red O for LDs, cytokine release was determined by ELISA, and the gene expression was analyzed by real-time PCR using TaqMan assays. Our data show that spikes induce LDs in PBMCs but not in HPMEC. In line, in PBMCs spike proteins lower expression of genes involving lipid metabolism and LDs 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 LDs formation in PBMCs seems to be not related to cell inflammatory activation. Further detailed studies are warranted to investigate in which specific immune cells spikes induce LDs, and what are pathophysiological mechanisms and consequences of this induction in vivo.

Keywords

recombinant spike protein; human PBMCs; lung microvascular endothelial cells; cytokines; chemokines; lipid droplets; lipid metabolism genes

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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