The myeloid immune signature of enterotoxigenic Bacteroides fragilis-induced murine colon tumorigenesis.

Autor: Thiele Orberg E; Oncology Department, Johns Hopkins University, Baltimore, Maryland, USA.; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA., Fan H; Oncology Department, Johns Hopkins University, Baltimore, Maryland, USA.; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA., Tam AJ; Oncology Department, Johns Hopkins University, Baltimore, Maryland, USA.; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA., Dejea CM; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA., Destefano Shields CE; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA., Wu S; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA., Chung L; Oncology Department, Johns Hopkins University, Baltimore, Maryland, USA.; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA.; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA., Finard BB; Oncology Department, Johns Hopkins University, Baltimore, Maryland, USA.; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA., Wu X; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA., Fathi P; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA., Ganguly S; Oncology Department, Johns Hopkins University, Baltimore, Maryland, USA.; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA., Fu J; Oncology Department, Johns Hopkins University, Baltimore, Maryland, USA.; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA., Pardoll DM; Oncology Department, Johns Hopkins University, Baltimore, Maryland, USA.; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA., Sears CL; Oncology Department, Johns Hopkins University, Baltimore, Maryland, USA.; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA., Housseau F; Oncology Department, Johns Hopkins University, Baltimore, Maryland, USA.; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA.
Jazyk: angličtina
Zdroj: Mucosal immunology [Mucosal Immunol] 2017 Mar; Vol. 10 (2), pp. 421-433. Date of Electronic Publication: 2016 Jun 15.
DOI: 10.1038/mi.2016.53
Abstrakt: Enterotoxigenic Bacteroides fragilis (ETBF), a human commensal and candidate pathogen in colorectal cancer (CRC), is a potent initiator of interleukin-17 (IL-17)-dependent colon tumorigenesis in Min Apc+/- mice. We examined the role of IL-17 and ETBF on the differentiation of myeloid cells into myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages, which are known to promote tumorigenesis. The myeloid compartment associated with ETBF-induced colon tumorigenesis in Min mice was defined using flow cytometry and gene expression profiling. Cell-sorted immature myeloid cells were functionally assayed for inhibition of T-cell proliferation and inducible nitric oxide synthase expression to delineate MDSC populations. A comparison of ETBF infection with that of other oncogenic bacteria (Fusobacterium nucleatum or pks + Escherichia coli) revealed a specific, ETBF-associated colonic immune infiltrate. ETBF-triggered colon tumorigenesis is associated with an IL-17-driven myeloid signature characterized by subversion of steady-state myelopoiesis in favor of the generation of protumoral monocytic-MDSCs (MO-MDSCs). Combined action of the B. fragilis enterotoxin BFT and IL-17 on colonic epithelial cells promoted the differentiation of MO-MDSCs, which selectively upregulated Arg1 and Nos2, produced NO, and suppressed T-cell proliferation. Evidence of a pathogenic inflammatory signature in humans colonized with ETBF may allow for the identification of populations at risk for developing colon cancer.
Databáze: MEDLINE
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