Pereira-Dutra et al. · bioRxiv (preprint) · 2025
SEPSIS-INDUCED LIPID DROPLET ACCUMULATION ENHANCES ANTIBACTERIAL INNATE IMMUNITY
Pereira-Dutra Filipe S., Santos Julia Cunha, Souza Ellen Kiarely, Savi Rodrigo Vieira, Souza Tamyris S., Espinheira-Silva Hugo, Ferraro-Moreira Felipe, Iack Guilherme, Cunha-Fernandes Tamires, Igreja-Silva Tathiany, Palhinha Lohanna, Campos Mariana Macedo, Oliveira Douglas Mathias, Cardoso Vinicius Soares, Rajao Matheus A., Teixeira Livia, Souza-Moreira Luciana, Costa Maria Fernanda Souza, Reis Patricia Alves, Bozza Patricia T.
The study
What was asked, and what was found
Pereira-Dutra et al., bioRxiv, 2025 asked whether the lipid droplets that pile up inside leukocytes during sepsis are a bystander of inflammation or part of the defence. The team followed triglyceride synthesis in Escherichia coli infected macrophages and in a mouse cecal ligation and puncture sepsis model, and put the question to DGAT1, the enzyme that makes the triglyceride the droplets are built from.
The genetic half of that test ran on AUM BioTech reagents. In primary mouse bone marrow derived macrophages the authors compared two ways of removing Dgat1. A conventional small interfering RNA carried in with a lipid transfection reagent reduced dgat1 expression by approximately 50%. A self-delivering AUMsilence sdASO against Dgat1 at 5 μM, catalogue code AUM-SIL-A-100-Dgat1-1, reached around 75% knockdown in the same primary cells, against the matching AUM scramble control AUM-SCR-A-100. The authors wrote that they proceeded with the self-delivering method because it was more effective, and every knockdown result in the paper comes from it.
With Dgat1 silenced and the macrophages then infected at a multiplicity of 100, lipid droplet accumulation fell, more bacteria survived inside the cell, and uptake was unchanged. The inflammatory output fell with it: prostaglandin E2, interleukin 6, CCL2, interferon beta and nitric oxide all dropped, as did inos and cox2 transcript, while lactate production and cell viability were untouched. Those results matched what the authors saw with a small molecule DGAT1 inhibitor, and together they place lipid droplet formation inside the antibacterial response rather than beside it. The in vivo sepsis experiments in this paper used the small molecule inhibitor, not the oligonucleotide.
Key findings
- In primary mouse bone marrow derived macrophages, an AUMsilence sdASO against Dgat1 at 5 μM reached around 75% knockdown, while a conventional siRNA carried in with a lipid transfection reagent reached approximately 50%, so the authors carried the self-delivering oligonucleotide forward for the rest of the study.(Results, page 19)
- Silencing Dgat1 with the AUMsilence sdASO cut the lipid droplet accumulation that Escherichia coli infection normally drives in macrophages, and left more bacteria inside the cell, without changing how much bacteria the cell took up.(Results, page 19)
- The same silencing lowered the inflammatory output of infected macrophages: prostaglandin E2, interleukin 6, CCL2, interferon beta and nitric oxide all fell, along with inos and cox2 transcript.(Results, page 19)
- The oligonucleotide result agreed with the small molecule result in the same paper, which is the cross-check that makes the target call stand.(Results, page 19)
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