耶尔森氏菌假结核通过造血 TLR-2 信号破坏肠道屏障完整性。
Yersinia pseudotuberculosis disrupts intestinal barrier integrity through hematopoietic TLR-2 signaling.
机构信息
Université Paris-Diderot, UMR843, Paris, France.
出版信息
J Clin Invest. 2012 Jun;122(6):2239-51. doi: 10.1172/JCI58147. Epub 2012 May 8.
Abstract
Intestinal barrier function requires intricate cooperation between intestinal epithelial cells and immune cells. Enteropathogens are able to invade the intestinal lymphoid tissue known as Peyer's patches (PPs) and disrupt the integrity of the intestinal barrier. However, the underlying molecular mechanisms of this process are poorly understood. In mice infected with Yersinia pseudotuberculosis, we found that PP barrier dysfunction is dependent on the Yersinia virulence plasmid and the expression of TLR-2 by hematopoietic cells, but not by intestinal epithelial cells. Upon TLR-2 stimulation, Y. pseudotuberculosis-infected monocytes activated caspase-1 and produced IL-1β. In turn, IL-1β increased NF-κB and myosin light chain kinase activation in intestinal epithelial cells, thus disrupting the intestinal barrier by opening the tight junctions. Therefore, Y. pseudotuberculosis subverts intestinal barrier function by altering the interplay between immune and epithelial cells during infection.
摘要
肠屏障功能需要肠上皮细胞和免疫细胞之间的精细合作。肠道病原体能够侵入称为派尔集合淋巴结（PPs）的肠道淋巴组织，并破坏肠道屏障的完整性。然而，这一过程的潜在分子机制尚不清楚。在感染假结核耶尔森菌的小鼠中，我们发现 PP 屏障功能障碍依赖于耶尔森氏菌毒力质粒和造血细胞表达的 TLR-2，但不依赖于肠上皮细胞。在 TLR-2 刺激下，假结核耶尔森菌感染的单核细胞激活了半胱天冬酶-1 并产生了白细胞介素-1β。反过来，白细胞介素-1β增加了 NF-κB 和肌球蛋白轻链激酶在肠上皮细胞中的激活，从而通过打开紧密连接来破坏肠道屏障。因此，假结核耶尔森氏菌通过在感染过程中改变免疫细胞和上皮细胞之间的相互作用来颠覆肠道屏障功能。
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