Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer

PLoS Pathogens

Henry J. McSorley¹  Sebastian Kollenda²  Matthias Epple²  Rick M. Maizels³  Jessica Gräb⁴  Jan Buer⁴  Wiebke Hansen⁴  Astrid M. Westendorf⁴  Eva Pastille⁴  Annika Frede⁴  Alexandra Adamczyk⁴  Robert Klopfleisch⁵ 

[1] Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom;Institute for Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Duisburg, Germany;Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom;Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany;Institute of Veterinary Pathology, Freie Universitaet Berlin, Berlin, Germany

关键词: Colon;    Helminth infections;    Mouse models;    T cells;    Colitis;    Regulatory T cells;    Inflammatory bowel disease;    Inflammation;   

DOI  :  10.1371/journal.ppat.1006649

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY