Institute of Microbiology, Infectious Diseases and Immunology, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Medical Faculty, Institute of Inflammation and Neurodegeneration, University Hospital Magdeburg, Magdeburg, Germany.
Front Cell Infect Microbiol. 2019 Apr 12;9:98. doi: 10.3389/fcimb.2019.00098. eCollection 2019.
We have recently shown that following peroral low-dose infection susceptible mice develop subacute ileitis within 10 days. Data regarding long-term intestinal and extra-intestinal sequelae of infection are scarce, however. We therefore challenged conventional C57BL/6 mice with one cyst of ME49 strain by gavage and performed a comprehensive immunopathological survey 10, 36, and 57 days later. As early as 10 days post-infection, mice were suffering from subacute ileitis as indicated by mild-to-moderate histopathological changes of the ileal mucosa. Furthermore, numbers of apoptotic and proliferating/regenerating epithelial cells as well as of T and B lymphocytes in the mucosa and lamina propria of the ileum were highest at day 10 post-infection, but declined thereafter, and were accompanied by enhanced pro-inflammatory mediator secretion in ileum, colon and mesenteric lymph nodes that was most pronounced during the early phase of infection. In addition, subacute ileitis was accompanied by distinct shifts in the commensal gut microbiota composition in the small intestines. Remarkably, immunopathological sequelae of infection were not restricted to the intestines, but could also be observed in extra-intestinal tissues including the liver, kidneys, lungs, heart and strikingly, in systemic compartments that were most prominent at day 10 post-infection. We conclude that the here provided long-term kinetic survey of immunopathological sequalae following peroral low-dose infection provides valuable corner stones for a better understanding of the complex interactions within the triangle relationship of (parasitic) pathogens, the host immunity and the commensal gut microbiota during intestinal inflammation. The low-dose infection model may be applied as valuable gut inflammation model in future pre-clinical studies in order to test potential treatment options for intestinal inflammatory conditions in humans.
我们最近表明，经口低剂量感染易感小鼠在 10 天内会发展为亚急性回肠炎。然而，关于感染的长期肠道和肠道外后遗症的数据却很少。因此，我们通过灌胃用 ME49 株的一个包囊挑战常规 C57BL/6 小鼠，并在 10、36 和 57 天后进行全面的免疫病理学调查。早在感染后 10 天，小鼠就患有亚急性回肠炎，回肠黏膜的组织病理学变化为轻度至中度。此外，感染后 10 天，回肠黏膜和固有层中凋亡和增殖/再生上皮细胞以及 T 和 B 淋巴细胞的数量最高，但此后下降，并伴有回肠、结肠和肠系膜淋巴结中促炎介质分泌增加，在感染早期最为明显。此外，亚急性回肠炎伴有肠道共生菌群组成的明显变化。值得注意的是，感染的免疫病理学后遗症不仅局限于肠道，还可以在包括肝脏、肾脏、肺、心脏在内的肠外组织中观察到，在感染后 10 天最为明显。我们得出结论，口服低剂量感染后免疫病理学后遗症的长期动力学研究为更好地理解（寄生虫）病原体、宿主免疫和肠道共生菌群在肠道炎症中的复杂相互作用提供了有价值的基石。低剂量感染模型可作为未来临床前研究中肠道炎症的有价值的肠道炎症模型，以测试人类肠道炎症疾病的潜在治疗选择。
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