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Schistosomiasis, caused by parasitic worms, affects over 250 million people globally, with limited treatment options due to praziquantel’s inability to prevent reinfection or reduce immunopathology. In Schistosoma mansoni ( S. mansoni ) infection, egg-induced granulomatous inflammation in the liver and intestines is driven by CD4 T helper (Th) cell responses, with severe pathology in some individuals mediated by Th17 cell activation. We previously demonstrated that the stimulator of interferon genes (STING) mitigates schistosome egg-induced immunopathology by promoting type I Interferon (IFN-I) production and suppressing Th17 responses. Here, we investigate the therapeutic potential of the STING agonist diABZI-3 in a high-pathology CBA mouse model. In vitro, diABZI-3 pretreatment of bone marrow-derived dendritic cells (BMDCs) significantly enhanced IFNβ production while abolishing IL-1β and IL-17 expression in response to schistosome egg stimulation, an effect dependent on early administration. In vivo, a single dose of diABZI-3 administered to S. mansoni -infected CBA mice reduced liver and intestine granuloma size, lowered IL-1β, IL-17, and CD209a levels, promoted the Foxp3⁺ regulatory T cells, reduced Th17 recruitment, and mitigated inflammation-associated shifts in gut microbiota populations. Furthermore, blocking STING degradation with bafilomycin A1 sustained STING signaling, leading to pronounced IL-1β suppression. These findings highlight diABZI-3 as a promising therapeutic agent for reducing schistosome-induced immunopathology.
Liu et al. (Fri,) studied this question.