Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model
Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model
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DOI：
10.1186/s13099-019-0306-9
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发表时间：
2019-05-17
期刊：
影响因子：
4.2
通讯作者：
Heimesaat, Markus M.
中科院分区：
文献类型：
--
作者：
Schmidt, Anna-Maria;Escher, Ulrike;Heimesaat, Markus M.
背景空肠弯曲杆菌感染是严重威胁人类健康的疾病，在世界范围内呈上升趋势。我们对宿主-病原体相互作用的分子机制的了解仍然有限。本课组建立了一种基于非生物IL-10（-/-）小鼠的临床空肠c感染模型，模拟了人类弯曲杆菌病的关键特征。为了进一步验证该模型在揭示急性疾病中病原体-宿主相互作用方面的作用，我们在这里调查了空肠梭菌重要毒力因子FlaA和FlaB以及主要粘连蛋白CadF（弯曲杆菌粘连蛋白）的免疫病理特征，它们分别在细菌运动、蛋白质分泌和粘连中起作用。方法和结果采用非生物IL-10（-/-）小鼠经口感染空肠C. 81-176菌株（WT）或其等基因flaA/B （flaA/B）或cadF （cadF）缺失突变体。培养分析显示，WT和cadF细菌稳定定植在胃、十二指肠和回肠中，而flaA/B细菌不稳定定植，而在感染后第6天，这三种细菌都在结肠中以相当高的负荷存在。值得注意的是，尽管flaA/B菌株的结肠定植密度很高，但小鼠感染flaA/B菌株并未导致明显的弯曲菌病，而感染cadF或WT的小鼠在感染后第6天出现急性小肠结肠炎。这些症状与明显的促炎免疫反应相吻合，不仅在肠道，而且在其他器官，如肝脏和肾脏，并伴有全身炎症反应，如空肠C. cadF或WT后血清MCP-1浓度升高，但没有flaA/B菌株感染。结论首次发现空肠C.鞭毛蛋白A/B在小鼠弯曲菌病的诱导中起重要作用，而非CadF介导的黏附作用。此外，继发性非生物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，而且适用于不同的空肠梭菌毒力因子在疾病诱导和进展中的作用的差异分析。
BackgroundCampylobacter 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 resultsTherefore, abiotic IL-10(-/-) mice were perorally infected with C. jejuni strain 81-176 (WT) or with its isogenic flaA/B (flaA/B) or cadF (cadF) deletion mutants. Cultural analyses revealed that WT and cadF but not flaA/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 flaA/B strain did not result in overt campylobacteriosis, whereas mice infected with cadF 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 cadF or WT, but not flaA/B strain infection.ConclusionFor 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.