Host responses to intestinal microbial antigens in gluten-sensitive mice.
Host responses to intestinal microbial antigens in gluten-sensitive mice.
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DOI：
10.1371/journal.pone.0006472
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发表时间：
2009-07-31
期刊：
影响因子：
3.7
通讯作者：
Verdú EF
中科院分区：
文献类型：
--
作者：
Natividad JM;Huang X;Slack E;Jury J;Sanz Y;David C;Denou E;Yang P;Murray J;McCoy KD;Verdú EF
通过可渗透性肠屏障过量摄取共生细菌抗原可能影响遗传易感宿主对特定抗原的反应。本研究的目的是探讨吲哚美辛治疗诱导的肠道屏障功能障碍是否影响谷蛋白致敏HLA-DQ8/HCD4小鼠肠道微生物群的宿主反应。用谷蛋白致敏HLA-DQ8/HCD4小鼠，用吲哚美辛加谷蛋白灌胃。采用Ussing法测定肠通透性；电镜观察上皮细胞（EC）超微结构；Q-real-time PCR检测连接蛋白编码基因的RNA表达体外抗原特异性t细胞增殖和细胞因子分析的免疫应答；荧光原位杂交法检测肠道菌群，血清表面染色法检测抗肠道菌群的全身抗体，然后进行FACS分析。吲哚美辛导致谷蛋白敏感小鼠肠道通透性明显增加。这些变化伴随着严重的EC损伤，e -钙粘蛋白RNA水平降低，脾细胞培养上清中IFN-γ升高，以及产生显著的针对肠道微生物群的IgM抗体。吲哚美辛增强谷蛋白诱导的屏障功能障碍和EC损伤，影响HLA-DQ8/HCD4小鼠的全身IFN-γ产生和宿主对肠道微生物群抗原的反应。结果表明，改变肠道屏障的环境因素可能通过对肠道微生物群的旁观者免疫激活使个体易患谷蛋白。
Excessive uptake of commensal bacterial antigens through a permeable intestinal barrier may influence host responses to specific antigen in a genetically predisposed host. The aim of this study was to investigate whether intestinal barrier dysfunction induced by indomethacin treatment affects the host response to intestinal microbiota in gluten-sensitized HLA-DQ8/HCD4 mice. HLA-DQ8/HCD4 mice were sensitized with gluten, and gavaged with indomethacin plus gluten. Intestinal permeability was assessed by Ussing chamber; epithelial cell (EC) ultra-structure by electron microscopy; RNA expression of genes coding for junctional proteins by Q-real-time PCR; immune response by in-vitro antigen-specific T-cell proliferation and cytokine analysis by cytometric bead array; intestinal microbiota by fluorescence in situ hybridization and analysis of systemic antibodies against intestinal microbiota by surface staining of live bacteria with serum followed by FACS analysis. Indomethacin led to a more pronounced increase in intestinal permeability in gluten-sensitized mice. These changes were accompanied by severe EC damage, decreased E-cadherin RNA level, elevated IFN-γ in splenocyte culture supernatant, and production of significant IgM antibody against intestinal microbiota. Indomethacin potentiates barrier dysfunction and EC injury induced by gluten, affects systemic IFN-γ production and the host response to intestinal microbiota antigens in HLA-DQ8/HCD4 mice. The results suggest that environmental factors that alter the intestinal barrier may predispose individuals to an increased susceptibility to gluten through a bystander immune activation to intestinal microbiota.
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