Fusobacterium nucleatum Infection of Colonic Cells Stimulates MUC2 Mucin and Tumor Necrosis Factor Alpha
Fusobacterium nucleatum Infection of Colonic Cells Stimulates MUC2 Mucin and Tumor Necrosis Factor Alpha
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DOI：
10.1128/iai.05118-11
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发表时间：
2011-07-01
影响因子：
3.1
通讯作者：
Chadee, Kris
中科院分区：
文献类型：
--
作者：
Dharmani, Poonam;Strauss, Jaclyn;Chadee, Kris
炎症性肠病的病因尚不完全清楚，但它受到正常肠道菌群存在以及尚未识别的病原体的影响。厌氧革兰氏阴性细菌种核梭杆菌是人类口腔和肠道的常见居民，其致病潜力各不相同。在这项研究中，我们证明，在人类结肠上皮细胞和大鼠结扎结肠环感染模型中，来自克罗恩病患者炎症肠道的高侵袭性核梭菌分离物比从非炎症肠道分离的微创菌株显著更高的MUC2和肿瘤坏死因子α (tnf - α)基因表达。只有活的核仁梭菌在直接接触和/或侵袭结肠细胞过程中诱导粘蛋白分泌和tnf - α表达。在大鼠结肠中，黏蛋白分泌在高侵袭性核梭菌分离物的反应中增加，但在微创菌株治疗中不受影响。综上所述，这些研究表明具核梭菌可能在肠道炎症性疾病的病因学中代表着一种具有挑战性的病原体，并突出了不同病原类型的候选细菌物种在疾病发病机制中的重要性。
The etiology of inflammatory bowel disease is not completely known, but it is influenced by the presence of normal gut microflora as well as yet-unrecognized pathogens. The anaerobic, Gram-negative bacterial species Fusobacterium nucleatum is a common resident of the human mouth and gut and varies in its pathogenic potential. In this study, we demonstrate that highly invasive F. nucleatum isolates derived from the inflamed guts of Crohn's disease patients evoked significantly greater MUC2 and tumor necrosis factor alpha (TNF-alpha) gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection. Only live F. nucleatum induced mucin secretion and TNF-alpha expression in direct contact with and/or during invasion of colonic cells. In rat colons, mucin secretion was augmented in response to a highly invasive F. nucleatum isolate but was unaffected by treatment with a minimally invasive strain. Taken together, these studies reveal that F. nucleatum may represent a challenging pathogen in the etiology of gut inflammatory diseases and highlight the importance of different pathotypes of candidate bacterial species in disease pathogenesis.