Distinct Pathophysiological Roles of Human Scavenger Receptors BI and BII in Mouse Abdominal Sepsis

Monday, March 23, 2026

9:00 AM - 10:00 AM Central Time

Location: Connections Central - RST 16

Naoki Hayase, n/a (he/him/his)

National Institutes of Health, Maryland

Disclosure(s): No relevant financial relationship(s) to disclose.
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Tatyana Vishnyakova, N/A

Senior Scientist
Department of Laboratory Medicine, Clinical Center, National Institutes of Health

Disclosure information not submitted.
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Irina Baranova, N/A

Senior Scientist
Department of Laboratory Medicine, Clinical Center, National Institutes of Health

Disclosure information not submitted.
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Alexander Bocharov, N/A

Staff Scientist
Department of Laboratory Medicine, Clinical Center, National Institutes of Health

Disclosure information not submitted.
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Xuzhen Hu, N/A

Biologist
Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health

Disclosure information not submitted.
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Thomas Eggerman, N/A

Program director
Department of Laboratory Medicine, Clinical Center, National Institutes of Health

Disclosure information not submitted.
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Peter Yuen, N/A

Staff Scientist
Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health

Disclosure information not submitted.
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Robert Star, N/A

Section Chief
Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health

Disclosure information not submitted.

Introduction: Dysregulated host immune response in sepsis is driven partly by pattern recognition receptors (PRRs). Class B scavenger receptors BI (SR-BI) and BII (SR-BII) are primarily involved in lipoprotein uptake; they can also bind and internalize bacteria. However, their roles in sepsis are unknown.

Methods: We overexpressed human SR-BI and BII (driven by pLiv-11) in the liver and to a lesser extent in the kidney. We performed cecal ligation and puncture (CLP) surgery, fully treated with fluids, antibiotics and analgesics, and followed mice for a 7d-survival study. We harvested blood, liver, kidneys, and adrenal glands 24h after CLP or 8h after intraperitoneal E.coli infusion. We conducted biochemical, histological, and microbiological assessment and evaluated inflammatory cytokine expression and vascular integrity. Mice were injected with green fluorescence protein (GFP)-labeled E. coli, which was detected by immunofluorescence in liver and kidneys.

Results: Human SR-BI and BII transgenic (Tg) mice had significantly worse 7d-survival compared to WT (SR-BI vs. WT, 6.3% vs. 33.3%, p = 0.001; SR-BII vs. WT, 6.3% vs. 33.3%, p = 0.001). 24 h after CLP, liver injury markers and histological damage were prominent in SR-B Tg mice, while kidney damage was comparable across the groups. Systemic inflammatory cytokines were markedly increased in SR-B Tg mice; parallel increases were seen in liver mRNA expression, not in kidney. Circulating vascular endothelial growth factor level was higher in SR-B Tg mice. SR-BI and BII overexpression dramatically decreased bacterial accumulation in liver. Immunofluorescence analyses revealed GFP-labeled E. coli localized within hepatic macrophages in SR-B Tg mice. In addition, these mice exhibited enhanced phagocytic activity and increased recruitment of macrophages. This tendency was more prominent in SR-BII Tg mice. Finally, overexpressed SR-BI remarkably reduced systemic high-density lipoprotein cholesterol level and lipid droplet storage in adrenal cortex, and dampened systemic corticosterone increase in response to septic insult.

Conclusions: Our findings suggest human SR-BI or BII overexpression contributes to higher mortality after CLP by excessive inflammatory response due to adrenal insufficiency (SR-BI) or hyperactive bacterial phagocytosis (SR-BII) in liver.