Authors
Mingwei Tong, Ge Liu, Guidong Ren, Wangxuan Zhang, Yuyu Qiao, Xiaodan Yang, Weiping Fan, Hui Yang, Yong Yang
Published in
PLoS pathogens. Volume 22. Issue 9. Pages e1014606. Epub Sep 25, 2026.
Abstract
Pro-inflammatory M1 polarization of adipose tissue macrophages (ATMs) drives adipose inflammation and obesity, suggesting that reprogramming ATM polarization holds therapeutic promise. Parasitic helminths have co-evolved with hosts to induce immune tolerance via M2 polarization, making helminth-derived M2-inducing molecules a potential therapeutic strategy against metabolic disorders. This study aimed to develop a defined serine protease inhibitor derived from Trichinella spiralis (Ts-SPI) as a novel immunomodulatory candidate against diet-induced metabolic disorders. In a high-fat diet (HFD)-induced obese mouse model, recombinant Ts-SPI (rTs-SPI) attenuated obesity and adipose tissue inflammation, and this effect was associated with its ability to reprogram macrophage polarization. In vitro studies confirmed that rTs-SPI drives phenotypic changes in both RAW264.7 cells and bone marrow-derived macrophages (BMDMs). Notably, a free fatty acid (FFA)-stimulated inflammatory adipocyte model and adoptive transfer assays demonstrated that rTs-SPI-reprogrammed macrophages mediate the anti-obesity and anti-inflammatory effects. Mechanistically, TIM-3 was identified as a key mediator through in vivo TIM-3 blockade assays. Pharmacological inhibition revealed downstream PI3K/AKT/mTOR signaling. In summary, this study identifies a parasite-derived protein as a potent TIM-3-targeting biologic candidate for treating metabolic inflammation, proposes a novel "helminth-inspired checkpoint modulation" strategy, and provides new insight into parasite-host immune crosstalk.
PMID:
42789571
Bibliographic data and abstract were imported from PubMed on 26 Sep 2026.
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