| First Author | Chung L | Year | 2018 |
| Journal | Cell Host Microbe | Volume | 23 |
| Issue | 2 | Pages | 203-214.e5 |
| PubMed ID | 29398651 | Mgi Jnum | J:272625 |
| Mgi Id | MGI:6285115 | Doi | 10.1016/j.chom.2018.01.007 |
| Citation | Chung L, et al. (2018) Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells. Cell Host Microbe 23(2):203-214.e5 |
| abstractText | Pro-carcinogenic bacteria have the potential to initiate and/or promote colon cancer, in part via immune mechanisms that are incompletely understood. Using Apc(Min) mice colonized with the human pathobiont enterotoxigenic Bacteroides fragilis (ETBF) as a model of microbe-induced colon tumorigenesis, we show that the Bacteroides fragilis toxin (BFT) triggers a pro-carcinogenic, multi-step inflammatory cascade requiring IL-17R, NF-kappaB, and Stat3 signaling in colonic epithelial cells (CECs). Although necessary, Stat3 activation in CECs is not sufficient to trigger ETBF colon tumorigenesis. Notably, IL-17-dependent NF-kappaB activation in CECs induces a proximal to distal mucosal gradient of C-X-C chemokines, including CXCL1, that mediates the recruitment of CXCR2-expressing polymorphonuclear immature myeloid cells with parallel onset of ETBF-mediated distal colon tumorigenesis. Thus, BFT induces a pro-carcinogenic signaling relay from the CEC to a mucosal Th17 response that results in selective NF-kappaB activation in distal colon CECs, which collectively triggers myeloid-cell-dependent distal colon tumorigenesis. |
