Department of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, Rostock University Medical Center, Rostock, Germany.
Front Immunol. 2023 Feb 24;14:1125912. doi: 10.3389/fimmu.2023.1125912. eCollection 2023.
The complexity of the spp. life cycle and their effective immune evasion strategies, makes vaccine development challenging. Unisexual infection models, that excludes any immunomodulatory effects of the parasite eggs, may contribute to a better understanding of complex immunological processes and identification of new targets for vaccine research. We have recently shown that long-term unisexual infection with schistosomes in mice results in an unpolarized Th1/Th2 response associated with an abnormally enlarged spleen and diffuse liver inflammation. Herein, we investigated whether (i) unisexual worms can mate after three months of single sex infection and (ii) thus the Th2 response induced by oviposition can reverse or heal the described systemic inflammation.
Therefore, we infected 6-8 weeks old female C57BL/6j mice with 100 male or female cercariae and reinfected with the opposite sex for the same period after 12 weeks. At 24 weeks after initial infection, we histologically examined worm mating, as evidenced by the presence of parasite eggs, infection-related pathology associated with eggs, and characterization of fibrosis in the livers.
Single worms are able to mate months after unisexual infection and start oviposition. Egg deposition has been associated with a typical Th2 immune response in the liver after unisexual reinfection, accompanied by increased recruitment of CD4+ T cells. Hepatic collagen levels were significantly increased in the reinfected groups compared to the naive and unisexually infected group.
Our results indicate that the eggs are able to restore the Th1/Th2 immune balance of a previous unisexual infection. However, the organ damage caused by the unisexual worms does not subside, but rather provides the baseline for the emerging egg-triggered inflammation and fibrosis. Since single schistosomes can mate even several weeks after unisexual infection and then accumulate worm- and egg-related organ damage, infection status without positive egg detection is very important, especially in areas with low prevalence.
由于 spp. 的生命周期复杂,且具有有效的免疫逃避策略,疫苗的开发具有挑战性。 排除寄生虫卵免疫调节作用的单性感染模型,可能有助于更好地理解复杂的免疫过程,并确定疫苗研究的新靶点。我们最近表明,在小鼠中长期单性感染血吸虫会导致非极化 Th1/Th2 反应,伴随脾脏异常增大和弥漫性肝脏炎症。在此,我们研究了(i)单性感染三个月后,单性蠕虫是否可以交配,以及(ii)由此产生的产卵引起的 Th2 反应是否可以逆转或治愈所述的全身炎症。
因此,我们用 100 个雄性或雌性尾蚴感染 6-8 周龄的 C57BL/6j 雌性小鼠,并在 12 周后用相同的性别的尾蚴进行相同时期的再次感染。在初次感染后 24 周,我们通过组织学检查证明了蠕虫交配,即存在寄生虫卵、与卵相关的感染相关病理学以及肝脏纤维化的特征。
单性感染数月后,单条蠕虫能够交配并开始产卵。再次单性感染后,卵沉积与肝脏中典型的 Th2 免疫反应相关,伴随着 CD4+T 细胞的募集增加。与未感染组和单性感染组相比,再次感染组的肝胶原水平显著增加。
我们的结果表明,卵能够恢复先前单性感染的 Th1/Th2 免疫平衡。然而,单性蠕虫引起的器官损伤并未消退,而是为新出现的卵触发的炎症和纤维化提供了基础。由于单条血吸虫甚至在单性感染数周后仍可交配,并累积与蠕虫和卵相关的器官损伤,因此没有阳性卵检测的感染状态非常重要,尤其是在流行率较低的地区。