Heimesaat Markus M, Mousavi Soraya, Bandick Rasmus, Bereswill Stefan
Gastrointestinal Microbiology Research Group, Institute of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203, Berlin, Germany.
Eur J Microbiol Immunol (Bp). 2022 Sep 7;12(3):73-83. doi: 10.1556/1886.2022.00014.
Gut microbiota depletion is a pivotal prerequisite to warrant Campylobacter jejuni infection and induced inflammation in IL-10-/- mice used as acute campylobacteriosis model. We here assessed the impact of an 8-week antibiotic regimen of ampicillin, ciprofloxacin, imipenem, metronidazole, and vancomycin (ABx) as compared to ampicillin plus sulbactam (A/S) on gut microbiota depletion and immunopathological responses upon oral C. jejuni infection. Our obtained results revealed that both antibiotic regimens were comparably effective in depleting the murine gut microbiota facilitating similar pathogenic colonization alongside the gastrointestinal tract following oral infection. Irrespective of the preceding microbiota depletion regimen, mice were similarly compromised by acute C. jejuni induced enterocolitis as indicated by comparable clinical scores and macroscopic as well as microscopic sequelae such as colonic histopathology and apoptosis on day 6 post-infection. Furthermore, innate and adaptive immune cell responses in the large intestines were similar in both infected cohorts, which also held true for intestinal, extra-intestinal and even systemic secretion of pro-inflammatory cytokines such as TNF-α, IFN-γ, and IL-6. In conclusion, gut microbiota depletion in IL-10-/- mice by ampicillin plus sulbactam is sufficient to investigate both, C. jejuni infection and the immunopathological features of acute campylobacteriosis.
肠道微生物群的耗竭是保证空肠弯曲菌感染并在用作急性弯曲菌病模型的IL-10基因敲除小鼠中诱发炎症的关键先决条件。我们在此评估了与氨苄西林加舒巴坦(A/S)相比,氨苄西林、环丙沙星、亚胺培南、甲硝唑和万古霉素(ABx)的8周抗生素方案对肠道微生物群耗竭以及口服空肠弯曲菌感染后的免疫病理反应的影响。我们获得的结果表明,两种抗生素方案在消耗小鼠肠道微生物群方面同样有效,在口服感染后促进了胃肠道相似的致病性定植。无论先前的微生物群耗竭方案如何,如感染后第6天的临床评分、大体及显微镜下后遗症(如结肠组织病理学和细胞凋亡)所示,小鼠同样受到急性空肠弯曲菌诱导的小肠结肠炎的影响。此外,两个感染组大肠中的先天性和适应性免疫细胞反应相似,对于促炎细胞因子如TNF-α、IFN-γ和IL-6的肠道、肠外甚至全身分泌情况也是如此。总之,氨苄西林加舒巴坦使IL-10基因敲除小鼠的肠道微生物群耗竭足以研究空肠弯曲菌感染和急性弯曲菌病的免疫病理特征。