Epstein-Barr virus worsens ulcerative colitis by triggering macrophage pyroptosis through glycolysis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurring inflammation and ulceration of the colon. While current treatments focus on suppressing the immune response, they often increase susceptibility to infections, including EBV. EBV infection has been linked to worse clinical outcomes in UC patients, but the underlying mechanisms remain poorly understood.

Researchers from West China Hospital, Sichuan University, have now uncovered how EBV exacerbates UC. The study, published in Precision Clinical Medicine, demonstrates that EBV infection activates pyroptosis—a form of programmed cell death—in intestinal macrophages by upregulating glycolysis. This process leads to the release of pro-inflammatory cytokines, which further damage the intestinal barrier and worsen colitis symptoms.

Using clinical samples from UC patients and a mouse model of colitis, the team found that EBV-induced macrophage pyroptosis was positively correlated with disease severity. In vitro experiments confirmed that EBV directly triggers pyroptosis in human macrophages, while in vivo studies showed that adoptive transfer of EBV-induced macrophages exacerbated colitis in mice. Importantly, inhibiting glycolysis with 2-deoxy-D-glucose (2-DG) blocked pyroptosis, suggesting a potential therapeutic strategy.