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Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer

Authors :
Anja Hafemann
Bo Hu
Eran Elinav
Liming Hao
Samuel Huber
Till Strowig
Richard A. Flavell
Stephanie C. Eisenbarth
Thomas F. Wunderlich
Chengcheng Jin
Claudia M. Wunderlich
Source :
Proceedings of the National Academy of Sciences. 110:9862-9867
Publication Year :
2013
Publisher :
Proceedings of the National Academy of Sciences, 2013.

Abstract

The microbiota is pivotal in the pathogenesis of inflammatory bowel disease (IBD)-associated inflammation-induced colorectal cancer (CRC), yet mechanisms for these effects remain poorly characterized. Here, we demonstrate that aberrant inflammasome-induced microbiota plays a critical role in CRC development, where mice deficient in the NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome feature enhanced inflammation-induced CRC formation. Intriguingly, WT mice cohoused either with inflammasome-deficient mice or with mice lacking IL-18 feature exacerbated inflammation-induced CRC compared with singly housed WT mice. Enhanced tumorigenesis is dependent on microbiota-induced chemokine (C-C motif) ligand 5 (CCL5)-driven inflammation, which in turn promotes epithelial cell proliferation through local activation of the IL-6 pathway, leading to cancer formation. Altogether, our results mechanistically link the altered microbiota with the pathogenesis of inflammation-induced CRC and suggest that in some conditions, microbiota components may transfer CRC susceptibility between individuals.

Details

ISSN :
10916490 and 00278424
Volume :
110
Database :
OpenAIRE
Journal :
Proceedings of the National Academy of Sciences
Accession number :
edsair.doi.dedup.....a52124ac65470e703b4e8a4ad190a272