Gölz Greta, Alter Thomas, Bereswill Stefan, Heimesaat Markus M
Institute of Food Hygiene, Freie Universität Berlin, Berlin, Germany.
Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
PLoS One. 2016 Jul 20;11(7):e0159685. doi: 10.1371/journal.pone.0159685. eCollection 2016.
Only limited information is available about the immunopathogenic properties of Arcobacter infection in vivo. Therefore, we performed a meta-analysis of published data in murine infection models to compare the pathogenic potential of Arcobacter butzleri with Campylobacter jejuni and commensal Escherichia coli as pathogenic and harmless reference bacteria, respectively.
METHODOLOGY / PRINCIPAL FINDINGS: Gnotobiotic IL-10-/- mice generated by broad-spectrum antibiotic compounds were perorally infected with A. butzleri (strains CCUG 30485 or C1), C. jejuni (strain 81-176) or a commensal intestinal E. coli strain. Either strain stably colonized the murine intestines upon infection. At day 6 postinfection (p.i.), C. jejuni infected mice only displayed severe clinical sequelae such as wasting bloody diarrhea. Gross disease was accompanied by increased numbers of colonic apoptotic cells and distinct immune cell populations including macrophages and monocytes, T and B cells as well as regulatory T cells upon pathogenic infection. Whereas A. butzleri and E. coli infected mice were clinically unaffected, respective colonic immune cell numbers increased in the former, but not in the latter, and more distinctly upon A. butzleri strain CCUG 30485 as compared to C1 strain infection. Both, A. butzleri and C. jejuni induced increased secretion of pro-inflammatory cytokines such as IFN-γ, TNF, IL-6 and MCP-1 in large, but also small intestines. Remarkably, even though viable bacteria did not translocate from the intestines to extra-intestinal compartments, systemic immune responses were induced in C. jejuni, but also A. butzleri infected mice as indicated by increased respective pro-inflammatory cytokine concentrations in serum samples at day 6 p.i.
CONCLUSION / SIGNIFICANCE: A. butzleri induce less distinct pro-inflammatory sequelae as compared to C. jejuni, but more pronounced local and systemic immune responses than commensal E. coli in a strain-dependent manner. Hence, data point towards that A. butzleri is more than a commensal in vertebrate hosts.
关于空肠弯曲菌感染在体内的免疫致病特性，目前仅有有限的信息。因此，我们对已发表的小鼠感染模型数据进行了荟萃分析，以比较布氏弯曲菌与空肠弯曲菌以及共生大肠杆菌（分别作为致病和无害参考细菌）的致病潜力。
方法/主要发现：通过广谱抗生素化合物产生的无菌IL-10基因敲除小鼠经口感染布氏弯曲菌（菌株CCUG 30485或C1）、空肠弯曲菌（菌株81-176）或共生肠道大肠杆菌菌株。感染后，任何一种菌株都能稳定地定殖于小鼠肠道。感染后第6天，空肠弯曲菌感染的小鼠仅表现出严重的临床后遗症，如消瘦性血性腹泻。严重疾病伴随着结肠凋亡细胞数量增加以及不同的免疫细胞群体，包括巨噬细胞和单核细胞、T细胞和B细胞以及致病性感染时的调节性T细胞。而布氏弯曲菌和大肠杆菌感染的小鼠在临床上未受影响，前者结肠免疫细胞数量增加，后者则未增加，与C1菌株感染相比，布氏弯曲菌CCUG 30485菌株感染时增加更为明显。布氏弯曲菌和空肠弯曲菌均诱导大肠和小肠中促炎细胞因子如IFN-γ、TNF、IL-6和MCP-1的分泌增加。值得注意的是，尽管活菌未从肠道转移到肠外腔室，但感染后第6天血清样本中促炎细胞因子浓度增加表明，空肠弯曲菌和布氏弯曲菌感染的小鼠均诱导了全身免疫反应。
结论/意义：与空肠弯曲菌相比，布氏弯曲菌诱导的促炎后遗症不那么明显，但比共生大肠杆菌以菌株依赖的方式引起更明显的局部和全身免疫反应。因此，数据表明布氏弯曲菌在脊椎动物宿主中不仅仅是一种共生菌。
