Experimental Pneumology, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research (DZL), Borstel, Germany.
Institute of Medical Microbiology and Hospital Epidemiology and German Center for Infection Research (DZIF), Partner Site Hannover, Hannover Medical School, Hannover, Germany.
Front Immunol. 2018 Nov 14;9:2614. doi: 10.3389/fimmu.2018.02614. eCollection 2018.
Countries with a high incidence of helminth infections are characterized by high morbidity and mortality to infections with intracellular pathogens such as . Some patients with - co-infections develop a so-called "chronic septicemic salmonellosis," with prolonged fever and enlargement of the liver and spleen. These effects are most likely due to the overall immunoregulatory activities of schistosomes such as induction of Tregs, Bregs, alternatively activated macrophages, and degradation of antibodies. However, detailed underlying mechanisms are not very well investigated. Here, we show that intraperitoneal application of live eggs prior to infection with Typhimurium in mice leads to an impairment of IFN-γ and IL-17 responses together with a higher bacterial load compared to infection alone. eggs were found in granulomas in the visceral peritoneum attached to the colon. Immunohistological staining revealed IPSE/alpha-1, a glycoprotein secreted from live schistosome eggs, and recruited basophils around the eggs. Noteworthy, IPSE/alpha-1 is known to trigger IL-4 and IL-13 release from basophils which in turn is known to suppress Th1/Th17 responses. Therefore, our data support a mechanism of how schistosomes impair a protective immune response against infection and increase our understanding of helminth-bacterial co-infections.
具有高寄生虫感染发生率的国家,其感染细胞内病原体(如)的发病率和死亡率较高。一些与寄生虫共同感染的患者会发展为所谓的“慢性败血性沙门氏菌病”,伴有长期发热、肝脏和脾脏肿大。这些影响很可能是由于血吸虫等寄生虫的整体免疫调节活性引起的,例如诱导 Tregs、Bregs、替代性激活的巨噬细胞和抗体降解。然而,详细的潜在机制尚未得到很好的研究。在这里,我们表明,在感染鼠伤寒沙门氏菌之前,将活血吸虫卵腹膜内给药会导致 IFN-γ 和 IL-17 反应受损,与单独感染相比,细菌负荷更高。在附着于结肠的内脏腹膜的肉芽肿中发现了虫卵。免疫组织化学染色显示,从活血吸虫卵中分泌的糖蛋白 IPSE/alpha-1,并招募卵周围的嗜碱性粒细胞。值得注意的是,IPSE/alpha-1 已知可从嗜碱性粒细胞中触发 IL-4 和 IL-13 的释放,而 IL-4 和 IL-13 又已知可抑制 Th1/Th17 反应。因此,我们的数据支持了血吸虫如何损害针对感染的保护性免疫反应的机制,并增加了我们对寄生虫-细菌共同感染的理解。