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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caco-2 Cells
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Caspase 1 / genetics
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Caspase 1 / immunology
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Enzyme Activation / genetics
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Enzyme Activation / immunology
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Hematopoietic Stem Cells / immunology*
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Hematopoietic Stem Cells / microbiology
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Hematopoietic Stem Cells / pathology
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Humans
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Interleukin-1beta / genetics
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Interleukin-1beta / immunology
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Intestinal Mucosa / immunology*
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Intestinal Mucosa / microbiology
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Intestinal Mucosa / pathology
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Mice
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Mice, Knockout
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Monocytes / immunology
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Monocytes / microbiology
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Monocytes / pathology
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Myosin-Light-Chain Kinase / genetics
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Myosin-Light-Chain Kinase / immunology
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NF-kappa B / genetics
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NF-kappa B / immunology
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Peyer's Patches / immunology*
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Peyer's Patches / microbiology
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Peyer's Patches / pathology
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Toll-Like Receptor 2 / genetics
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Toll-Like Receptor 2 / immunology*
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Yersinia pseudotuberculosis / genetics
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Yersinia pseudotuberculosis / immunology*
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Yersinia pseudotuberculosis Infections / genetics
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Yersinia pseudotuberculosis Infections / immunology*
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Yersinia pseudotuberculosis Infections / pathology
Substances
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Interleukin-1beta
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NF-kappa B
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Tlr2 protein, mouse
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Toll-Like Receptor 2
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Myosin-Light-Chain Kinase
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Caspase 1