Publikationsdatenbank

Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer (2017)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Pastille, Eva

Frede, Annika

McSorley, Henry J.

Gräb, Jessica

Adamczyk, Alexandra

Kollenda, Sebastian

Hansen, Wiebke

Epple, Matthias

Buer, Jan

Maizels, Rick M.

Klopfleisch, Robert (WE 12)

Westendorf, Astrid M.

Quelle

PLoS pathogens

Bandzählung: 13

Heftzählung: 9

Seiten: Artikel e1006649

ISSN: 1553-7374

Sprache

Englisch

Verweise

URL (Volltext): https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006649

DOI: 10.1371/journal.ppat.1006649

Pubmed: 28938014

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.