Karout Iman, Salhab Zahraa, Sherri Nour, Bitar Elio R, Borghol Abdul Hamid, Sabra Hady, Kassem Aya, Osman Omar, Alam Charbel, Znait Sabah, Assaf Rayan, Fadlallah Sukayna, Jurjus Abdo, Hashash Jana G, Rahal Elias A
Department of Experimental Pathology, Immunology, and Microbiology, American University of Beirut, Beirut 1107-2020, Lebanon.
Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon.
Viruses. 2024 Apr 17;16(4):624. doi: 10.3390/v16040624.
Epstein-Barr virus (EBV), a family member, is associated with an increased risk of autoimmune disease development in the host. We previously demonstrated that EBV DNA elevates levels of the pro-inflammatory cytokine IL-17A and that inhibiting Toll-like receptor (TLR) 3, 7, or 9 reduces its levels. Moreover, this DNA exacerbated colitis in a mouse model of inflammatory bowel disease (IBD). In the study at hand, we examined whether inhibition of TLR3, 7, or 9 alleviates this exacerbation. Mice were fed 1.5% dextran sulfate sodium (DSS) water and administered EBV DNA. Then, they were treated with a TLR3, 7, or 9 inhibitor or left untreated. We also assessed the additive impact of combined inhibition of all three receptors. Mice that received DSS, EBV DNA, and each inhibitor alone, or a combination of inhibitors, showed significant improvement. They also had a decrease in the numbers of the pathogenic colonic IL-17A+IFN-γ+ foci. Inhibition of all three endosomal TLR receptors offered no additive benefit over administering a single inhibitor. Therefore, inhibition of endosomal TLRs reduces EBV DNA exacerbation of mouse colitis, offering a potential approach for managing IBD patients infected with EBV.
爱泼斯坦-巴尔病毒（EBV）是疱疹病毒家族成员，与宿主自身免疫性疾病发生风险增加相关。我们之前证明，EBV DNA会升高促炎细胞因子白细胞介素-17A（IL-17A）的水平，而抑制Toll样受体（TLR）3、7或9可降低其水平。此外，这种DNA会加剧炎症性肠病（IBD）小鼠模型中的结肠炎。在本研究中，我们检测了抑制TLR3、7或9是否能减轻这种加剧作用。给小鼠喂食1.5%的葡聚糖硫酸钠（DSS）水并给予EBV DNA。然后，用TLR3、7或9抑制剂对它们进行治疗，或不进行治疗。我们还评估了联合抑制所有三种受体的叠加影响。单独接受DSS、EBV DNA和每种抑制剂，或抑制剂组合的小鼠均表现出显著改善。它们结肠中致病性IL-17A+IFN-γ+病灶数量也有所减少。抑制所有三种内体TLR受体相比单独使用一种抑制剂并无叠加益处。因此，抑制内体TLR可减轻EBV DNA对小鼠结肠炎的加剧作用，为治疗感染EBV的IBD患者提供了一种潜在方法。
