Cystic echinococcosis (CE) is a severe zoonotic parasitic disease caused by the larval stage of Echinococcus granulosus sensu lato (E. granulosus s.l.), a tapeworm that predominantly infects herbivores and humans (dead-end hosts) (Wen et al., 2019). CE posed significant threats to human health and caused substantial economic losses to the livestock industry (Woolsey and Miller, 2021). In terms of pathogenesis, E. granulosus s.l. Has evolved sophisticated mechanisms to circumvent host immune response (Siracusano et al., 2012). Excretory-secretory products (ESPs) from E. granulosus s.l. Played crucial roles in the host-parasite interaction, contributing to regulation of the host immune system (Brehm and Koziol, 2017; Pan et al., 2017, 2018; Santos et al., 2016). Macrophages were generally considered as crucial roles in host immune system as the first responders to infection (Wynn et al., 2013). Macrophages were classified into classically activated macrophages (M1) and alternatively activated macrophages (M2) based on their characteristics (Laskin et al., 2011; Wynn et al., 2013). M1 macrophages exert a pivotal role in combating parasite infections by engaging in phagocytosis, antigen presentation, and the production of inflammatory cytokines as well as effector molecules (Chen and Zhang, 2017). During the later stages of parasitic infection, M2 macrophages contribute to the regulation of inflammation, mitigating damage, facilitating tissue repair and immune modulation (Gordon and Martinez, 2010). Meanwhile, the metacestode of E. granulosus s.l. Exhibits complex and diverse immune modulation mechanisms against host macrophages (Amri and Touil-Boukoffa, 2015; Dong et al., 2019; Lin et al., 2021; Mejri et al., 2017; Sagasti et al., 2021; Seoane et al., 2016; Silva-Alvarez et al., 2016; Wang et al., 2019).

Parasite annexins (ANXs) represent important targets for vaccine and drug development (Hofmann et al., 2010). In parasitic organisms, certain ANXs not only serve as structural proteins to maintain parasite stability (Hofmann et al., 2010), but also participate in host-parasite interaction such as regulating host immune responses (Gao et al., 2007; He et al., 2014; Yan et al., 2008). Certain E. granulosus s.l. ANXs (EgANXs) found in extracellular vesicles (EVs) from E. granulosus s.l. Are likely secreted through the EV pathway and participate in host-parasite interactions (Marcilla et al., 2012; Nicolao et al., 2019; Wu et al., 2021; Yang et al., 2021). The annexins B18 from E. granulosus s.l. (EgANXB18), as a highly abundant secreted protein in the small extracellular vesicles secreted by the protoscoleces (PSCs) of E. granulosus s.l. (Wu et al., 2021), has the ability to regulate the immune function of peripheral blood mononuclear cells (PBMCs) in mice (He et al., 2023). Therefore, EgANXB18 holds significant potential and warrants focused further investigation. However, the impact of EgANXB18 on macrophages, which are closely associated with PBMCs, has not been investigated. The aim of this study was to evaluate the impact of recombinant EgANXB18 (rEgANXB18) on the metabolic activity, polarization, and inflammatory response of mouse macrophages. The results will contribute to a deeper understanding of the mechanisms involved in the interaction between E. granulosus s.l. And its intermediate host.