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Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria

Abstract

Penetration of the gut mucosa by pathogens expressing invasion genes is believed to occur mainly through specialized epithelial cells, called M cells, that are located in Peyer's patches. However, Salmonella typhimurium that are deficient in invasion genes encoded by Salmonella pathogenicity island 1 (SPI1) are still able to reach the spleen after oral administration. This suggests the existence of an alternative route for bacterial invasion, one that is independent of M cells. We report here a new mechanism for bacterial uptake in the mucosa tissues that is mediated by dendritic cells (DCs). DCs open the tight junctions between epithelial cells, send dendrites outside the epithelium and directly sample bacteria. In addition, because DCs express tight-junction proteins such as occludin, claudin 1 and zonula occludens 1, the integrity of the epithelial barrier is preserved.

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Figure 1: DCs induce transcytosis of fluorescent bacteria across a monolayer of differentiated human Caco-2 cells.
Figure 2: DCs cross the filter and infiltrate the epithelial monolayer.
Figure 3: DCs can uptake bacteria directly through a monolayer of epithelial cells.
Figure 4: DCs express proteins involved in the formation of TJs.
Figure 5: DCs are recruited at the site of infection in vivo.
Figure 6: In the presence of bacteria, DCs creep between epithelial cells and send dendrites out to the intestinal lumen in vivo.
Figure 7: DCs are recruited in the intestine and can also uptake nonpathogenic E. coli.
Figure 8: Scheme of the events occurring during a bacterial infection.

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Acknowledgements

We thank K. Giese (Atugen, Berlin) for the TaqMan analysis on occludin mRNA and R. Steinman and D. Grdic for helpful discussions. Supported by grants from the Italian Association against Cancer (AIRC); the National Research Council (CNR Project in Biotechnology); the EC contract MUCIMM; and the Swiss National Science Foundation.

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Correspondence to Paola Ricciardi-Castagnoli.

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Rescigno, M., Urbano, M., Valzasina, B. et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2, 361–367 (2001). https://doi.org/10.1038/86373

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