Background Campylobacter jejuni infections constitute serious threats to human health with increasing prevalences worldwide. Our knowledge regarding the molecular mechanisms underlying host-pathogen interactions is still limited. Our group has established a clinical C. jejuni infection model based on abiotic IL-10-/- mice mimicking key features of human campylobacteriosis. In order to further validate this model for unraveling pathogen-host interactions mounting in acute disease, we here surveyed the immunopathological features of the important C. jejuni virulence factors FlaA and FlaB and the major adhesin CadF (Campylobacter adhesin to fibronectin), which play a role in bacterial motility, protein secretion and adhesion, respectively. Methods and results Therefore, abiotic IL-10-/- mice were perorally infected with C. jejuni strain 81-176 (WT) or with its isogenic flaA/B (ΔflaA/B) or cadF (ΔcadF) deletion mutants. Cultural analyses revealed that WT and ΔcadF but not ΔflaA/B bacteria stably colonized the stomach, duodenum and ileum, whereas all three strains were present in the colon at comparably high loads on day 6 post-infection. Remarkably, despite high colonic colonization densities, murine infection with the ΔflaA/B strain did not result in overt campylobacteriosis, whereas mice infected with ΔcadF or WT were suffering from acute enterocolitis at day 6 post-infection. These symptoms coincided with pronounced pro-inflammatory immune responses, not only in the intestinal tract, but also in other organs such as the liver and kidneys and were accompanied with systemic inflammatory responses as indicated by increased serum MCP-1 concentrations following C. jejuni ΔcadF or WT, but not ΔflaA/B strain infection. Conclusion For the first time, our observations revealed that the C. jejuni flagellins A/B, but not adhesion mediated by CadF, are essential for inducing murine campylobacteriosis. Furthermore, the secondary abiotic IL-10-/- infection model has been proven suitable not only for detailed investigations of immunological aspects of campylobacteriosis, but also for differential analyses of the roles of distinct C. jejuni virulence factors in induction and progression of disease.

中文翻译：

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在临床鼠感染模型中评估的空肠弯曲杆菌鞭毛蛋白和粘附素 CadF 的免疫病理学特性。

背景 空肠弯曲杆菌感染对人类健康构成严重威胁，在世界范围内的流行率不断增加。我们对宿主-病原体相互作用的分子机制的了解仍然有限。我们小组建立了基于非生物IL-10-/-小鼠模拟人类弯曲杆菌病关键特征的临床空肠弯曲杆菌感染模型。为了进一步验证该模型用于揭示急性疾病中病原体-宿主相互作用，我们在此调查了重要的空肠弯曲杆菌毒力因子 FlaA 和 FlaB 以及主要粘附素 CadF（弯曲杆菌粘附素至纤连蛋白）的免疫病理学特征，它们发挥了分别在细菌运动、蛋白质分泌和粘附中发挥作用。方法和结果因此，非生物IL-10-/-小鼠经口感染C. 空肠菌株 81-176 (WT) 或其同基因 flaA/B (ΔflaA/B) 或 cadF (ΔcadF) 缺失突变体。文化分析显示，WT 和 ΔcadF 而不是 ΔflaA/B 细菌稳定地定植于胃、十二指肠和回肠，而所有三种菌株在感染后第 6 天以相当高的负荷存在于结肠中。值得注意的是，尽管结肠定植密度高，小鼠感染 ΔflaA/B 菌株不会导致明显的弯曲杆菌病，而感染 ΔcadF 或 WT 的小鼠在感染后第 6 天患有急性小肠结肠炎。这些症状与明显的促炎免疫反应相吻合，不仅在肠道中，而且在肝脏和肾脏等其他器官中，并伴有全身炎症反应，如 C. 空肠 ΔcadF 或 WT，但不是 ΔflaA/B 菌株感染。结论 我们的观察首次揭示了空肠弯曲杆菌鞭毛蛋白 A/B，而不是由 CadF 介导的粘附，对于诱导小鼠弯曲杆菌病至关重要。此外，二次非生物 IL-10-/- 感染模型已被证明不仅适用于弯曲杆菌病免疫学方面的详细研究，而且适用于不同空肠弯曲杆菌毒力因子在疾病诱导和进展中的作用的差异分析。