Echinococcus granulosus antigen B regulates the macrophage cGAS–STING pathway to mitigate myocardial ischemia–reperfusion injury

Background Myocardial ischemia–reperfusion (IR) injury is a critical complication in patients with myocardial infarction following the restoration of coronary blood flow. Echinococcus granulosus cyst fluid protein antigen B ( Eg AgB) is known to modulate host immune response. This study investigates whether the recombinant antigen B subunit 2 (r Eg AgB8/2) can mitigate IR injury by suppressing inflammation and promoting myocardial tissue repair. Methods An IR injury model was induced by ligating the left anterior descending (LAD) coronary artery for 1 h, followed by 24 h reperfusion. Recombinant Eg AgB8/2 protein expressed in E. coli was administered intraperitoneally at the onset of reperfusion to evaluate its therapeutic potential. After 24 h of reperfusion, cardiac function and injury were assessed using echocardiography, TTC/Evans Blue staining, and histopathological analysis. Protein and mRNA levels of cytokines (TNF-α, IL-6, IL-10, and TGF-β) in sera and cardiac tissue were quantified using ELISA and RT-qPCR, respectively. In vitro studies, cytokine secretion in bone marrow-derived macrophages (BMDMs) culture supernatants was measured by ELISA. Macrophage polarization was evaluated via flow cytometry by identifying surface markers for M1 (CD86⁺) and M2 (CD206⁺) phenotypes. Expression levels of proteins in the cGAS/STING/p-TBK1/p-IRF3 signaling pathway in both myocardial tissues and BMDMs were detected by Western blotting. Results Treatment with r Eg AgB8/2 significantly improved cardiac function and reduced myocardial injury markers (LDH, CK-MB) and infarct size in mice with IR injury. Compared to untreated IR controls, r Eg AgB8/2 treatment significantly reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in both serum and cardiac tissue, and downregulated the M1 macrophage marker iNOS in cardiac tissue. Concurrently, it increased the expression of anti-inflammatory cytokines (IL-10 and TGF-β) in serum and cardiac tissue, along with upregulating the M2 macrophage marker Arg-1 in cardiac tissue. This reduction in the inflammatory response in IR-injured cardiac tissue was associated with enhanced polarization toward the M2 macrophage phenotype. In vitro studies further showed that r Eg AgB8/2 promotes M2 macrophage polarization associated with reduced activation of the cGAS/STING/TBK1/IRF3 signaling pathway. Conclusions r Eg AgB8/2 promotes macrophage polarization toward M2 phenotype in a manner associated with suppression of the cGAS/STING/TBK1/IRF3 signaling pathway to attenuate myocardial IR injury and associated inflammation. It provides a novel therapeutic strategy for ischemia–reperfusion injury and related inflammatory diseases.