Hayes Kelly S, Cliffe Laura J, Bancroft Alison J, Forman Simon P, Thompson Seona, Booth Cath, Grencis Richard K
School of Biological Sciences, FBMH, MAHSC, University of Manchester, Manchester, United Kingdom.
Wellcome Trust Centre for Cell Matrix Research, University of Manchester, Manchester, United Kingdom.
PLoS Negl Trop Dis. 2017 Jun 26;11(6):e0005708. doi: 10.1371/journal.pntd.0005708. eCollection 2017 Jun.
Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris) is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+) mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.
在肠道线虫感染患病率也很高的发展中国家,与感染相关的癌症发病率正在上升。毛首鞭形线虫(T. muris)是一种寄生于小鼠肠道的线虫,是人类毛首鞭形线虫(T. trichiura)的直接模型,而毛首鞭形线虫是人类主要的土壤传播蠕虫感染之一。为了评估毛首鞭形线虫的慢性感染是否确实会影响癌症特征的发展,野生型小鼠和结肠癌模型(APC min/+)小鼠都感染了这种寄生虫。野生型小鼠的寄生虫感染导致了肿瘤性变化的发展,类似于用致癌物偶氮甲烷处理过的小鼠所出现的变化。此外,APCmin/+小鼠的慢性和急性感染都导致了肿瘤发展的增强,这种增强与感染部位不同,表明是系统性控制。通过阻断这些小鼠中寄生虫诱导的T调节反应,感染后肿瘤数量的增加被消除。因此,仅毛首鞭形线虫感染就会导致肠道病变增加,而肠道病变是已知的癌症标志物,同时也会增加结肠癌模型中肿瘤形成的发生率。因此,寄生虫感染对癌症发展的影响可能很大。