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Astragalus polysaccharides protects against acute leptospirosis by glycolysis-depended priming effect
Wenlong Zhang1, Ning Song2, Yuan Gao2
1Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, People's Republic of China; Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, People's Republic of China.
Abstract:
Leptospirosis, caused by pathogenic leptospira, is a neglected infectious disease that causes acute kidney injury, bleeding disorders, and even death. People can become infected with leptospirosis when they travel into epidemic areas. Except for vaccines and antibiotics, there are few reports of other drugs about prevention of leptospirosis. In this study, we show that the natural molecular compound, astragalus polysaccharides (APS), prevents against acute leptospirosis in hamsters. Pretreatment with APS improved the survival rate of hamsters with more minor organ damage and lower leptospira burden. After pretreatment with APS, the expression levels of leptospira-induced TLR2, TLR4, and TNF-α were enhanced. The priming effect of APS was studied in vitro. The data showed that leptospira-induced expressions of TNF-α and IL-1β were higher in APS-primed peritoneal macrophage, with enhanced glucose consumption and lactate production. Transcriptomic analysis revealed that pretreatment with APS down regulated respiratory chain and mitochondrial function, up regulated glycolysis related gene expressions. After pretreatment with glycolysis inhibitor (2-DG), the priming effect of APS in leptospira infection was inhibited. Our results indicated that pretreatment with natural molecular compound, APS, protected against acute leptospirosis in hamsters by priming effect through enhanced glycolysis.
Insights
Astragalus polysaccharides (APS) offer a natural defense against leptospirosis. This study shows APS pretreatment enhances hamster survival by boosting immune responses and altering cellular metabolism, specifically through increased glycolysis.
Area of Science:
- Immunology
- Infectious Diseases
- Natural Products
Background:
- Leptospirosis is a severe infectious disease with limited preventive options beyond vaccines and antibiotics.
- Pathogenic Leptospira causes significant organ damage, bleeding disorders, and mortality.
- Natural compounds are being explored for novel therapeutic and preventive strategies against neglected diseases.
Purpose of the Study:
- To investigate the protective effects of astragalus polysaccharides (APS) against acute leptospirosis.
- To elucidate the underlying mechanisms of APS-mediated protection, focusing on immune priming and metabolic alterations.
- To evaluate APS as a potential preventive agent for leptospirosis.
Main Methods:
- Hamsters were pretreated with APS before challenge with pathogenic Leptospira.
- Survival rates, organ damage, and bacterial burden were assessed.
- In vitro studies on peritoneal macrophages examined immune mediator expression (TLR2, TLR4, TNF-α, IL-1β) and metabolic activity (glucose consumption, lactate production).
- Transcriptomic analysis identified key metabolic pathways affected by APS, including glycolysis and mitochondrial respiration.
- The role of glycolysis was confirmed using a glycolysis inhibitor (2-DG).
Main Results:
- APS pretreatment significantly improved hamster survival rates and reduced organ damage and leptospira burden.
- APS enhanced the expression of leptospira-induced immune mediators like TLR2, TLR4, and TNF-α.
- In vitro, APS-primed macrophages showed heightened responses to Leptospira, with increased TNF-α and IL-1β production.
- APS pretreatment led to upregulated glycolysis and downregulated mitochondrial respiration, as revealed by transcriptomic analysis.
- Inhibition of glycolysis abolished the protective priming effect of APS.
Conclusions:
- Astragalus polysaccharides (APS) demonstrate significant protective effects against acute leptospirosis in a hamster model.
- APS confers protection by priming the immune system and enhancing glycolysis, rather than suppressing the pathogen directly.
- The findings suggest APS is a promising natural compound for leptospirosis prevention by modulating host metabolic and immune responses.
