# Antigen B from Echinococcus granulosus regulates autophagy-mediated macrophage polarization to alleviate immune thrombocytopenia

## TL;DR

This study shows that a parasite-derived protein, Antigen B, can reduce symptoms of immune thrombocytopenia by altering macrophage behavior through autophagy.

## Contribution

The novel finding is that Antigen B from Echinococcus granulosus regulates autophagy to shift macrophage polarization, offering a new therapeutic approach for ITP.

## Key findings

- AgB reduces hemorrhage and increases platelet counts in ITP mouse models.
- AgB inhibits M1 macrophage polarization and enhances autophagy flux in macrophages.
- AgB modulates LC3II/LC3I and p62 to promote autophagosome formation and clearance.

## Abstract

Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a low platelet count (< 100 × 109/L) induced by an autoimmune mechanism, which increases platelet clearing by macrophages. Antigen B (AgB) is a lipoprotein derived from Echinococcus granulosus larvae and has been observed to modulate host immunity. This study evaluated the mechanistic impact of AgB on macrophage polarization in the ITP mouse model.

This study analyzed blood samples acquired from pediatric patients with ITP and healthy controls. Furthermore, the levels of inflammatory cytokines in plasma, as well as macrophage surface markers and autophagy-related markers [microtubule-associated protein 1 light chain 3 (LC3) and sequestosome-1 (p62)] in peripheral blood mononuclear cells (PBMCs) were evaluated. Moreover, the ITP model was successfully established after immunization with an anti-CD41 antibody and treatment with AgB in vivo. Platelet counts and hemorrhagic symptoms were continuously examined, while plasma inflammatory cytokine levels and the expression of pertinent indicators in the spleen were assessed. RAW264.7 macrophages and lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were treated with AgB to assess the expression of relevant markers in an in vitro experiment. The mechanism by which AgB regulates LC3 and p62 levels to inhibit LPS-induced macrophages was investigated. Lastly, autophagy inhibitors were administered to evaluate the specific stage of autophagy affected by AgB.

AgB ameliorated hemorrhage and increased platelet counts in ITP murine models while decreasing the M1/M2 macrophage ratio. AgB therapy increased macrophage autophagic flux in vivo and in vitro. To elucidate the effects of AgB on various stages of autophagy, macrophages were treated with two autophagy inhibitors: 3-methyladenine (3-MA) and bafilomycin A1. This study revealed that AgB primarily acts by influencing the expression of LC3II/LC3I and p62, increasing the formation of autophagosomes and enabling lysosomes to identify and consume autophagosomes more accurately. AgB also inhibits macrophage polarization towards M1. These results suggested that AgB reduced hemorrhage in the ITP mouse model by regulating autophagy-mediated macrophage polarization.

This study showed that AgB alleviates ITP by restoring autophagy flux, inhibiting M1 macrophage polarization, and modulating immunity.

The online version contains supplementary material available at 10.1186/s13071-025-07182-3.