Campylobacter jejuni infection induces acute enterocolitis in IL-10-/- mice pretreated with ampicillin plus sulbactam.

Markus M Heimesaat, Soraya Mousavi, Rasmus Bandick, Stefan Bereswill
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Abstract

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.

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空肠弯曲菌感染会诱发用氨苄西林加舒巴坦预处理的 IL-10-/- 小鼠急性小肠结肠炎。
肠道微生物群耗竭是保证空肠弯曲菌感染的关键前提,也是IL-10-/-小鼠作为急性弯曲菌病模型诱发炎症的关键前提。我们在此评估了氨苄西林、环丙沙星、亚胺培南、甲硝唑和万古霉素(ABx)与氨苄西林加舒巴坦(A/S)的 8 周抗生素方案对空肠弯曲菌口服感染后肠道微生物群耗竭和免疫病理反应的影响。我们的研究结果表明,这两种抗生素方案在消耗小鼠肠道微生物群方面的效果相当,都能在口腔感染后促进类似的致病菌在胃肠道内定植。无论采用哪种微生物群清除方案,小鼠在感染后第 6 天都会受到空肠大肠杆菌诱发的急性小肠结肠炎的类似损害,表现为临床评分、宏观和微观后遗症,如结肠组织病理学和细胞凋亡。此外,两组感染者大肠内的先天性和适应性免疫细胞反应相似,肠内、肠外甚至全身分泌的促炎细胞因子(如 TNF-α、IFN-γ 和 IL-6)也相似。总之,通过氨苄西林加舒巴坦来消耗 IL-10-/- 小鼠的肠道微生物群足以研究空肠弯曲杆菌感染和急性弯曲杆菌病的免疫病理特征。
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