To investigate the pharmacological effect of STING agonists in schistosomiasis
Research Poster Health & Life Sciences 2025 Graduate ExhibitionPresentation by Pengyu Liu
Exhibition Number 174
Abstract
Schistosomiasis is the second most prevalent parasitic disease around the world. The infection with Schistosoma mansoni causes morbidity and mortality via a pathogenic host CD4+ T cell-mediated immune response directed against parasite egg antigens. We have previously demonstrated that low-pathology Wild-Type C57BL/6 (BL/6) mice lacking Stimulator of Interferon genes (STING) exhibited markedly enhanced hepatic granulomatous inflammation associated with significantly increased Th1 and Th17 cytokines. Additionally, high-pathology CBA mice have severe liver granulomatous inflammation due to enhanced proinflammatory gene expression and reduced STING expression. Taken together, we hypothesized that the STING agonist, diABZI-3, would control the pro-inflammatory cytokine production by activating STING in the high pathology model of schistosomiasis. Here, our results showed that diABZI-3 mitigated liver inflammation and induced robust IFN production, while IL-1B and IL-17 were impaired in the CBA mouse model. On the other hand, activation of STING using STING agonist in the BL/6 mouse model led to a significant increase in IFN and IL-1B production and enhanced immunopathology. Our findings suggest that STING activation works as a double-edged sword: STING activation is important in alleviating inflammation, but over-activating STING might lead to a pro-inflammatory environment. STING agonists may serve as a novel therapeutic strategy to restrain schistosome immunopathology.
Importance
Schistosomiasis is the second most prevalent parasitic disease worldwide. The current treatment, praziquantel, targets the adult worms; and emerging resistance to this drug poses a significant challenge. These studies will provide the basis for the use of small molecule STING agonists as immunomodulators of schistosomiasis and other immune-mediated diseases. These studies can help us understand whether STING can be used as a target for immunotherapy. Thus, the development of new therapeutic approaches is increasingly important in the face of drug resistance and vaccine failure