The myeloid immune signature of enterotoxigenic Bacteroides fragilis-induced murine colon tumorigenesis.
The myeloid immune signature of enterotoxigenic Bacteroides fragilis-induced murine colon tumorigenesis.
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作者：
肠促炎性脆弱拟杆菌（ETBF）是一种人源性和结肠直肠癌（CRC）的候选病原体，是MinApc+/-小鼠中IL-17依赖性结肠肿瘤发生的有效引发剂。我们研究了IL-17和ETBF对髓系细胞分化为髓系来源的抑制细胞（MDSC）和肿瘤相关巨噬细胞（TAM）的作用，这些细胞已知可促进肿瘤发生。使用流式细胞术和基因表达谱分析确定了Min小鼠中与ETBF诱导的结肠肿瘤发生相关的髓样区室。功能性地测定细胞分选的未成熟骨髓细胞对T细胞增殖和iNOS表达的抑制，以描绘MDSC群体。ETBF感染与其他致癌细菌（具核梭杆菌或pks+ E.大肠杆菌）显示了一个特定的，ETBF相关的结肠免疫浸润。ETBF触发的结肠肿瘤发生与IL-17驱动的髓样特征相关，其特征在于稳态骨髓生成的颠覆有利于产生前肿瘤单核细胞（MO）-MDSC。脆弱类杆菌肠毒素BFT和IL-17对结肠上皮细胞的联合作用促进了MO-MDSCs的分化，MO-MDSCs选择性上调Arg 1和Nos 2，产生NO并抑制T细胞增殖。在ETBF定殖的人类中致病性炎症特征的证据可以允许鉴定处于发展结肠癌风险的人群。
Enterotoxigenic Bacteroides fragilis (ETBF), a human commensal and candidate pathogen in colorectal cancer (CRC), is a potent initiator of IL-17-dependent colon tumorigenesis in MinApc+/-mice. We examined the role of IL-17 and ETBF on the differentiation of myeloid cells into myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM), 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 iNOS expression in order to delineate MDSC populations. A comparison of ETBF infection to that of other oncogenic bacteria (Fusobacterium nucleatum or pks+ E. 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 (MO)-MDSCs. Combined action of the Bacteroides 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.
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影响因子：
17.1
作者：
Highfill SL;Cui Y;Giles AJ;Smith JP;Zhang H;Morse E;Kaplan RN;Mackall CL
通讯作者：
Mackall CL
影响因子：
11.2
作者：
Tosolini, Marie;Kirilovsky, Amos;Galon, Jerome
通讯作者：
Galon, Jerome
影响因子：
11.2
作者：
Housseau F;Wu S;Wick EC;Fan H;Wu X;Llosa NJ;Smith KN;Tam A;Ganguly S;Wanyiri JW;Iyadorai T;Malik AA;Roslani AC;Vadivelu JS;Van Meerbeke S;Huso DL;Pardoll DM;Sears CL
通讯作者：
Sears CL
DOI：
10.4049/jimmunol.0902574
发表时间：
2010-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
He D;Li H;Yusuf N;Elmets CA;Li J;Mountz JD;Xu H
通讯作者：
Xu H
促炎S100蛋白调节髓样衍生的抑制细胞的积累。
DOI：
10.4049/jimmunol.181.7.4666
发表时间：
2008-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Sinha P;Okoro C;Foell D;Freeze HH;Ostrand-Rosenberg S;Srikrishna G
通讯作者：
Srikrishna G