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Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer
PLoS Pathogens ( IF 5.5 ) Pub Date : 2017-09-22 , DOI: 10.1371/journal.ppat.1006649
Eva Pastille , Annika Frede , Henry J. McSorley , Jessica Gräb , Alexandra Adamczyk , Sebastian Kollenda , Wiebke Hansen , Matthias Epple , Jan Buer , Rick M. Maizels , Robert Klopfleisch , Astrid M. Westendorf

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host’s immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs). This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation. On the contrary, specific parasite infections are well known to be directly linked to carcinogenesis. Whether a helminth infection interferes with the development of colitis-associated colon cancer (CAC) is not yet known. In the present study, we demonstrate that the treatment of mice with the intestinal helminth Heligmosomoides polygyrus at the onset of tumor progression in a mouse model of CAC does not alter tumor growth and distribution. In contrast, H. polygyrus infection in the early inflammatory phase of CAC strengthens the inflammatory response and significantly boosts tumor development. Here, H. polygyrus infection was accompanied by long-lasting alterations in the colonic immune cell compartment, with reduced frequencies of colonic CD8+ effector T cells. Moreover, H. polygyrus infection in the course of dextran sulfate sodium (DSS) mediated colitis significantly exacerbates intestinal inflammation by amplifying the release of colonic IL-6 and CXCL1. Thus, our findings indicate that the therapeutic application of helminths during CAC might have tumor-promoting effects and therefore should be well-considered.



中文翻译:

肠蠕虫感染可导致结肠炎相关结肠癌的致癌作用

炎症性肠病(IBD)是胃肠道的慢性炎症性疾病,与大肠癌发展的风险增加密切相关。由蠕虫引起的寄生虫感染已显示可通过释放免疫调节分子并诱导调节性T细胞(Tregs)来调节宿主的免疫反应。宿主中激发的这种免疫抑制状态被认为是治疗IBD患者和减轻急性肠道炎症的一种新颖且有希望的方法。相反,众所周知,特定的寄生虫感染与致癌作用直接相关。蠕虫感染是否会干扰与结肠炎相关的结肠癌(CAC)的发展尚不清楚。在本研究中,我们证明了肠道蠕虫对小鼠的治疗Heligmosomoides polygyrus在CAC小鼠模型中的肿瘤进展开始时不会改变肿瘤的生长和分布。相反,H。在CAC炎性初期,多发感染可增强炎性反应,并显着促进肿瘤的发展。在这里,H多头回感染伴有结肠免疫细胞区室的长期改变,并降低了结肠CD8 +效应T细胞的频率。此外,H一夫多妻硫酸右旋糖酐钠(DSS)介导的结肠炎感染可通过放大结肠IL-6和CXCL1的释放显着加重肠道炎症。因此,我们的发现表明,CAC期间蠕虫的治疗应用可能具有促肿瘤作用,因此应予以充分考虑。

更新日期:2017-09-23
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