Targeted deletion of MyD88 in intestinal epithelial cells results in compromised antibacterial immunity associated with downregulation of polymeric immunoglobulin receptor, mucin-2, and antibacterial peptides.
Targeted deletion of MyD88 in intestinal epithelial cells results in compromised antibacterial immunity associated with downregulation of polymeric immunoglobulin receptor, mucin-2, and antibacterial peptides.
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作者：
肠上皮细胞（IEC）形成物理和免疫屏障，将大量肠道微生物群与宿主组织分开。 MyD88 依赖性 Toll 样受体信号传导是微生物与宿主相互作用的关键介质。我们通过产生具有 IEC 靶向删除 Myd88 基因 (MyD88ΔIEC) 的小鼠来检查上皮 MyD88 表达的作用。上皮 MyD88 信号传导的丧失导致粘液相关细菌数量增加；细菌（包括机会性病原体肺炎克雷伯菌）易位至肠系膜淋巴结；减少跨粘膜电阻；粘液相关抗菌活性受损；聚合免疫球蛋白受体（上皮 IgA 转运蛋白）、mucin-2（肠道粘液的主要蛋白）以及抗菌肽 RegIIIγ 和 Defa-rs1 的表达下调。我们进一步观察到 MyD88ΔIEC 小鼠和野生型同窝小鼠肠道微生物群组成的显着差异。这些身体、免疫和微生物缺陷导致 MyD88ΔIEC 小鼠对实验性结肠炎的易感性增加。我们得出结论，IEC 中的 MyD88 信号传导对于维持肠道稳态至关重要。
Intestinal epithelial cells (IECs) form a physical and immunological barrier that separates the vast gut microbiota from host tissues. MyD88-dependent Toll-like receptor signaling is a key mediator of microbial–host cross-talk. We examined the role of epithelial MyD88 expression by generating mice with an IEC-targeted deletion of the Myd88 gene (MyD88ΔIEC). Loss of epithelial MyD88 signaling resulted in increased numbers of mucus-associated bacteria; translocation of bacteria, including the opportunistic pathogen Klebsiella pneumoniae, to mesenteric lymph nodes; reduced transmucosal electrical resistance; impaired mucus-associated antimicrobial activity; and downregulated expression of polymeric immunoglobulin receptor (the epithelial IgA transporter), mucin-2 (the major protein of intestinal mucus), and the antimicrobial peptides RegIIIγ and Defa-rs1. We further observed significant differences in the composition of the gut microbiota between MyD88ΔIEC mice and wild-type littermates. These physical, immunological, and microbial defects resulted in increased susceptibility of MyD88ΔIEC mice to experimental colitis. We conclude that MyD88 signaling in IECs is crucial for maintenance of gut homeostasis.
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影响因子：
29.4
作者：
Asquith MJ;Boulard O;Powrie F;Maloy KJ
通讯作者：
Maloy KJ
DOI：
10.1152/ajpgi.00328.2004
发表时间：
2005-05-01
影响因子：
4.5
作者：
Fukata, M;Michelsen, KS;Abreu, MT
通讯作者：
Abreu, MT
影响因子：
2.1
作者：
Guo, Yaqian;Hastie, Trevor;Tibshirani, Robert
通讯作者：
Tibshirani, Robert
影响因子：
8
作者：
通讯作者：
--
影响因子：
8.6
作者：
Gong, Jianfeng;Xu, Jingyue;Li, Jieshou
通讯作者：
Li, Jieshou