Intestinal colonization with IL-10 inducing adherent E. coli protects from intestinal inflammation and tumor development

Autor: Gretchen Diehl, Daniel Zegarra Ruiz, Dasom Kim, Kendra Norwood, Andrea A. Hill, Fatima Beatriz Saldana Morales
Rok vydání: 2020
Předmět:
Zdroj: The Journal of Immunology. 204:233.7-233.7
ISSN: 1550-6606
0022-1767
Popis: Colorectal cancer (CRC) is the third most common and third most deadly cancer in the US. Chronic intestinal inflammation corresponds with advanced disease stage and decreased survival in CRC. Intestinal inflammation corresponds with changes in the microbiota, including expanded proteobacteria, such as E. coli. This altered microbiota is thought to support inflammation and disease progression in both CRC and inflammatory bowel disease (IBD). However, how individual microbes interact with host cells and the pathways they activate remains incompletely defined. We characterized immune effects after colonization with individual isolates from a panel of human mucosally associated E. coli. In contrast to our expectations, a subset induced intestinal macrophage production of IL-10, protecting from colitis. Further characterization of a single isolate revealed colonization with this isolate limited tumor incidence in a model of inflammation associated colorectal tumors. Intestinal macrophages, macrophage production of IL-10, and epithelial expression of IL-10 receptor were all required for anti-inflammatory and anti-tumor effects. Colonization with an isogenic mutant E. coli that lacked a single gene important for epithelial attachment did not induce IL-10 and amplified intestinal tumors with increased tumor infiltration of anti-inflammatory immune cells. While the inherent diversity of the microbiota makes it difficult to pinpoint singular pathways of tumorigenesis, we have identified a regulatory loop between adherent microbes, intestinal epithelium and intestinal immune cells which promotes barrier integrity and limits tumor development, identifying novel ways to therapeutically target inflammation and CRC.
Databáze: OpenAIRE
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