<b>A unique intestinal desensitization strategy: Blocking membrane protease enrichment on macrophages by helminth-derived cystatin-like protein</b>

Egg allergies are prevalent worldwide and pose serious risks in children; however, a permanent cure is lacking. The desensitization of <i>Trichinella spiralis</i>-secreted cystatin-like protein (Ts-CLP) is an alternative to helminthic therapy for food allergies. Based on the allergy model in which <i>Escherichia coli</i> (<i>E. coli</i>) delivers ovalbumin (OVA) to the digestive system of OT-II mice, various therapeutic interventions related to Ts-CLP partially (delayed bone marrow-derived macrophages (BMDMs) intervention) or completely relieved inflammation and the disease course. Mechanistically, protein‒macrophage interaction-mediated blockade of the membrane enrichment of plasmin was identified as the main mode by which Ts-CLP-induced regulation manifests as high-level immunosuppressive cytokine secretion and impaired T-cell recruitment. In summary, Ts-CLP-incubated BMDMs can serve as an alternative for inflammation intervention in OVA-induced intestinal allergic diseases and the strategy of blocking protease enrichment on cell membrane is feasible to be applied in the treatment of type II inflammatory diseases.