The protective effect and mechanism of bacterial lipoprotein training in endotoxemic mice via upregulation of citraconic acid levels

doi:10.13418/j.issn.1001-165x.2026.5.06

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Chinese Journal of Clinical Anatomy ›› 2026, Vol. 44 ›› Issue (5) : 534-542. DOI: 10.13418/j.issn.1001-165x.2026.5.06

The protective effect and mechanism of bacterial lipoprotein training in endotoxemic mice via upregulation of citraconic acid levels

Xu Xiujuan^1,2, Wan Yantong¹, Chen Wenhan¹, Hong Yinghao¹, Huang Xiaolan³, Yan Zhengzheng³, Liu Jinghua¹*

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Abstract

Objective To investigate the metabolic characteristics of macrophages trained by bacterial lipoprotein (BLP) and the protective effect of the upregulated metabolite citraconic acid against endotoxemia in mice and its underlying mechanism. Methods Using metabolomic profiling, we characterized the metabolic rewiring of BLP‑primed macrophages in response to S.aureus infection, and dissected the mechanisms by which citraconic acid exerts direct antibacterial effects, potentiates macrophage killing and clearance, and mitigates inflammatory cascades, ultimately conferring survival benefit in endotoxemic mice. Results BLP training significantly enhanced the mitochondrial spare respiratory capacity and glycolytic rate of macrophages, accompanied by elevated levels of glycolytic and tricarboxylic acid (TCA) cycle metabolites. Anti-inflammatory metabolites, including itaconic acid and citraconic acid, were also increased. citraconic acid exerted direct bacteriostatic effects, potentiated the phagocytic and bactericidal capacities of macrophages, and suppressed LPS-induced inflammatory cytokine production. Furthermore, citraconic acid markedly improved the 7-day survival rate in endotoxemic mice, and reduced serum levels of inflammatory cytokines, as well as ALT, AST, BUN, and Cr. Conclusions BLP training induces metabolic reprogramming in macrophages. Citraconic acid protects endotoxemic mice through mechanisms involving anti-inflammatory, anti-infective, and anti-organ damage activities.

Key words

BLP training / / / Endotoxemia / / / Macrophages / / / Citraconic acid

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Xu Xiujuan, Wan Yantong, Chen Wenhan, Hong Yinghao, Huang Xiaolan, Yan Zhengzheng, Liu Jinghua. The protective effect and mechanism of bacterial lipoprotein training in endotoxemic mice via upregulation of citraconic acid levels[J]. Chinese Journal of Clinical Anatomy. 2026, 44(5): 534-542 https://doi.org/10.13418/j.issn.1001-165x.2026.5.06

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