Antigen B from Echinococcus granulosus regulates macrophage phagocytosis by controlling TLR4 endocytosis in immune thrombocytopenia

• Published in: Chemico-biological interactions 2024-12, Vol.406, p.111350, Article 111350
• Main Authors: Zhang, Yunfei, Yue, Yingbin, Cheng, Yongfeng, Jiao, Hongjie, Yan, Mei
• Format: Article
• Language: English
• Subjects: Echinococcus granulosus; Immune thrombocytopenia; Macrophage phagocytosis; Macrophage polarization; TLR4 endocytosis
• ISSN: 0009-2797; 1872-7786; 1872-7786
• DOI: 10.1016/j.cbi.2024.111350

Immune thrombocytopenia (ITP) is characterized by a reduction in platelet counts, stemming from an autoimmune-mediated process where platelets are excessively cleared by macrophages. This enhanced phagocytosis is a cardinal pathogenic mechanism in ITP. Antigen B (AgB), a principal component of the Echinococcus granulosus cyst fluid, plays a pivotal role in safeguarding the parasite from host immune defenses by modulating macrophage activation. In this study, we explored the potential of AgB to regulate macrophage activation in the context of ITP. Our observations indicated a diminished presence of M1 macrophages and a reduced phagocytic capacity in patients infected with E. granulosus sensu stricto. We isolated AgB from E. granulosus cyst fluid (EgCF) and discovered that it could suppress the polarization of M1 macrophages and weaken their phagocytic activity via Fcγ receptors, consequently alleviating thrombocytopenia in an ITP mouse model. At the molecular level, AgB was found to suppress the activation of nuclear factor kappa B (NF-κB) and interferon regulatory factor 3 (IRF3) by impeding their nuclear translocation, leading to a reduction in the generation of inflammatory cytokines. Furthermore, AgB was shown to inhibit Toll-like receptor 4 (TLR4) endocytosis and the recycling of CD14. In aggregate, our findings uncover a novel immunomodulatory mechanism of AgB, which suppresses macrophage phagocytosis by regulating TLR4 endocytosis and the subsequent activation of NF-κB and IRF3 signaling pathways. These insights shed new light on the molecular intricacies of E. granulosus-induced immune evasion and suggest that AgB may serve as a promising therapeutic agent for ITP. [Display omitted] •AgB from Echinococcus granulosus cyst fluid inhibits M1 macrophage polarization and phagocytosis via Fcγ receptors.•AgB inhibited Toll like receptor 4 (TLR4) endocytosis and CD14 recycling.•AgB reduces the activation of NF-κB and IRF3 by reducing their nuclear translocation.•AgB ameliorates thrombocytopenia in mice with Immune thrombocytopenia (ITP).